@article {11156, title = {Factor structure of the Harmonized Cognitive Assessment Protocol neuropsychological battery in the Health and Retirement Study}, journal = {Neuropsychology}, year = {Forthcoming}, abstract = {Objectives: The Harmonized Cognitive Assessment Protocol (HCAP) describes an assessment battery and a family of population-representative studies measuring neuropsychological performance. We describe the factorial structure of the HCAP battery in the US Health and Retirement Study (HRS).Method: The HCAP battery was compiled from existing measures by a cross-disciplinary and international panel of researchers. The HCAP battery used in the 2016 wave of the HRS. We used factor analysis methods to assess and refine a theoretically-driven single and multiple domain factor structure for tests included in the HCAP battery among 3,347 participants with evaluable performance data. Results: For the eight domains of cognitive functioning identified theoretically (orientation, memory [immediate, delayed, \& recognition], set shifting, attention/speed, language/fluency, andvisuospatial), all single factor models fit reasonably well, although four of these domains had either 2 or 3 indicators where good fit is axiomatic. Multidimensional models suggested the eight-domain model was overly complex. A five-domain model (orientation, memory delayed and recognition, executive functioning, language/fluency, visuospatial) was identified as a reasonable model for summarizing performance in this sample (standardized root mean square residual = 0.05, root mean square error of approximation = 0.05, confirmatory fit index = 0.94). Discussion: The HCAP battery conforms adequately to a multidimensional structure of neuropsychological performance. The derived measurement models can be used as anchors for calibrating cross-national studies of cognitive performance, and to identify persons performing atthe low end as part of an algorithmic classification of probable dementia}, keywords = {Cognitive Ability, Confirmatory Factor Analysis, HCAP, Older Adults}, doi = {10.31234/osf.io/rvmhj}, author = {Richard N Jones and Jennifer J Manly and Kenneth M. Langa and Lindsay H Ryan and Deborah A Levine and Ryan J McCammon and David R Weir} } @article {13526, title = {Harmonization of Later-Life Cognitive Function Across National Contexts: Results from the Harmonized Cognitive Assessment Protocols (HCAPs).}, journal = {medRxiv}, year = {Forthcoming}, abstract = {

BACKGROUND: The Harmonized Cognitive Assessment Protocol (HCAP) is an innovative instrument for cross-national comparisons of later-life cognitive function, yet its suitability across diverse populations is unknown. We aimed to harmonize general and domain-specific cognitive scores from HCAPs across six countries, and evaluate precision and criterion validity of the resulting harmonized scores.

METHODS: We statistically harmonized general and domain-specific cognitive function across the six publicly available HCAP partner studies in the United States, England, India, Mexico, China, and South Africa (N=21,141). We used an item banking approach that leveraged common cognitive test items across studies and tests that were unique to studies, as identified by a multidisciplinary expert panel. We generated harmonized factor scores for general and domain- specific cognitive function using serially estimated graded-response item response theory (IRT) models. We evaluated precision of the factor scores using test information plots and criterion validity using age, gender, and educational attainment.

FINDINGS: IRT models of cognitive function in each country fit well. We compared measurement reliability of the harmonized general cognitive function factor across each cohort using test information plots; marginal reliability was high (r> 0{\textperiodcentered}90) for 93\% of respondents across six countries. In each country, general cognitive function scores were lower with older ages and higher with greater levels of educational attainment.

INTERPRETATION: We statistically harmonized cognitive function measures across six large, population-based studies of cognitive aging in the US, England, India, Mexico, China, and South Africa. Precision of the estimated scores was excellent. This work provides a foundation for international networks of researchers to make stronger inferences and direct comparisons of cross-national associations of risk factors for cognitive outcomes.

FUNDING: National Institute on Aging (R01 AG070953, R01 AG030153, R01 AG051125, U01 AG058499; U24 AG065182; R01AG051158).

}, keywords = {Cognition, Education, harmonization, HCAP}, doi = {10.1101/2023.06.09.23291217}, author = {Gross, Alden L and LI, CHIHUA and Brice{\~n}o, Emily M and Renter{\'\i}a, Miguel Arce and Richard N Jones and Kenneth M. Langa and Jennifer J Manly and Nichols, Emma L and David R Weir and Wong, Rebeca and Berkman, Lisa and Lee, Jinkook and Lindsay C Kobayashi} } @article {9168, title = {Heterogeneity in polygenic scores for common human traits}, journal = {bioRxiv}, year = {Forthcoming}, abstract = {This study investigates the creation of polygenic scores (PGS)s for human population research. PGSs are a linear, usually weighted, combination of risk alleles that estimate the cumulative genetic risk of an individual for a particular trait. While conceptually simple, there are numerous ways to estimate PGSs, not all achieving the same end goals. In this paper, we systematically investigate the impact of four key decisions in the building of PGSs from published genome-wide association meta-analysis results: 1) whether to use single nucleotide polymorphisms (SNPs) assessed by imputation, 2) criteria for selecting which SNPs to include in the score, 3) whether to account for linkage disequilibrium (LD), and 4) if accounting for LD, which type of method best captures the correlation structure among SNPs (i.e. clumping vs. pruning). Using the Health and Retirement Study (HRS), a nationally representative, population-based longitudinal panel study of Americans over the age of 50, we examine the predictive ability as well as the variability and co-variability in PGSs arising from these different estimation approaches. We examine four traits with large published and replicated genome-wide association studies (height, body mass index, educational attainment, and depression). Our central finding demonstrates PGSs that include all available SNPs either explain the most amount of variation in an outcome or are not significantly different than the PGSs that does. Thus, for reproducibility through rigor and transparency, we recommend that researchers include a PGS with all available SNPs as a reference, and provide substantial justification for using alternative methods.}, keywords = {Genetics, Heterogeneity, PGS}, doi = {10.1101/106062}, author = {Erin B Ware and Lauren L Schmitz and Jessica Faul and Arianna M Gard and Colter Mitchell and Wei Zhao and David R Weir and Sharon L R Kardia} } @article {13370, title = {Assessing the First Economic Impact Payment in the Older Population Using the Health and Retirement Study}, number = {rb454}, year = {2023}, institution = {Michigan Retirement and Disability Research Center, University of Michigan}, address = {Ann Arbor, Michigan}, keywords = {economic impact, Impact payment}, url = {https://mrdrc.isr.umich.edu/pubs/assessing-the-first-economic-impact-payment-in-the-older-population-using-the-health-and-retirement-study-2/}, author = {G{\'a}bor K{\'e}zdi and David R Weir} } @article {13185, title = {Assessing the First Economic Impact Payment in the Older Population Using the Health and Retirement Study}, year = {2023}, institution = {University of Michigan}, address = {Ann Arbor, Michigan}, abstract = {We use data collected by the Health and Retirement Study in its 2020 wave to study awareness and the impact of the Economic Impact Payment stimulus on different groups of older Americans during the coronavirus pandemic.}, keywords = {economic impact, older population}, url = {https://mrdrc.isr.umich.edu/publications/papers/pdf/wp454.pdf}, author = {G{\'a}bor K{\'e}zdi and David R Weir} } @article {12477, title = {A cultural neuropsychological approach to harmonization of cognitive data across culturally and linguistically diverse older adult populations.}, journal = {Neuropsychology}, volume = {37}, year = {2023}, pages = {247-257}, abstract = {

OBJECTIVE: To describe a cultural neuropsychological approach to prestatistical harmonization of cognitive data across the United States (U.S.) and Mexico with the Harmonized Cognitive Assessment Protocol (HCAP).

METHOD: We performed a comprehensive review of the administration, scoring, and coding procedures for each cognitive test item administered across the English and Spanish versions of the HCAP in the Health and Retirement Study (HRS) in the U.S. and the Ancillary Study on Cognitive Aging in Mexico (Mex-Cog). For items that were potentially equivalent across studies, we compared each cognitive test item for linguistic and cultural equivalence and classified items as confident or tentative linking items, based on the degree of confidence in their comparability across cohorts and language groups. We evaluated these classifications using differential item functioning techniques.

RESULTS: We evaluated 132 test items among 21 cognitive instruments in the HCAP across the HRS and Mex-Cog. We identified 72 confident linking items, 46 tentative linking items, and 14 items that were not comparable across cohorts. Measurement invariance analysis revealed that 64\% of the confident linking items and 83\% of the tentative linking items showed statistical evidence of measurement differences across cohorts.

CONCLUSIONS: Prestatistical harmonization of cognitive data, performed by a multidisciplinary and multilingual team including cultural neuropsychologists, can identify differences in cognitive construct measurement across languages and cultures that may not be identified by statistical procedures alone. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

}, keywords = {cognitive data, HCAP, Mex-Cog, neuropsychology}, issn = {1931-1559}, doi = {10.1037/neu0000816}, author = {Brice{\~n}o, Emily M and Arce Renter{\'\i}a, Miguel and Gross, Alden L and Richard N Jones and Gonzalez, Christopher and Wong, Rebeca and David R Weir and Kenneth M. Langa and Jennifer J Manly} } @article {13588, title = {Decision Making for Patients With Severe Dementia Versus Normal Cognition Near the End of Life.}, journal = {Innovation in Aging}, volume = {7}, year = {2023}, pages = {igad081}, abstract = {

BACKGROUND AND OBJECTIVES: The clinical progression of severe dementia frequently leads to situations where surrogate decision makers must quickly make choices about potentially burdensome treatments that offer limited clinical benefit. We examined whether the number of decision makers and their access to advance directives were related to treatment choice for patients with severe dementia in comparison to those with normal cognition.

RESEARCH DESIGN AND METHODS: We retrospectively linked survey responses about end-of-life treatment decisions to Medicare claims for Health and Retirement Study respondents dying between 2002 and 2015 whose next-of-kin reported a need for surrogate decision making. We estimated multivariable logistic regression models to study measures of aggressive care in the last 6 months of life; in-hospital death, burdensome transfers, and burdensome treatments.

RESULTS: Compared to patients who were cognitively normal near the end of life ( = 1 198), patients with severe dementia ( = 722) were less likely to experience burdensome treatments (18\% [95\% confidence interval {CI} 14-21] vs 32\% [95\% CI 29-35]), burdensome transfers (20\% [95\% CI 17-24] vs 30\% [95\% CI 27-33]), and in-hospital death (24\% [95\% CI 20-28] vs 30\% [95\% CI 26-33]) when surrogates were involved. Rates of burdensome treatments, transfers, or in-hospital death for decedents with severe dementia did not vary with single versus multiple decision makers or when decision makers were informed by advance directives. However, among decedents with normal cognition, a single decision maker informed by an advance directive was associated with the lowest rates of burdensome treatments and in-hospital death.

DISCUSSION AND IMPLICATIONS: Surrogate decision makers made similar choices around end-of-life care for patients with severe dementia regardless of the number of decision makers and availability of advance directives. However, both advance directives and single decision makers were associated with less aggressive care for cognitively normal decedents.

}, keywords = {Advance care planning, cognitive impairment, family caregivers}, issn = {2399-5300}, doi = {10.1093/geroni/igad081}, author = {Nicholas, Lauren Hersch and Halpern, Scott D and David R Weir and Baum, Micah Y and Nolan, Marie and Gallo, Joseph and Kenneth M. Langa} } @article {13668, title = {Documentation of lnterleukin-6 (IL-6) Assays from Dried Blood Spots 2014 and 2016}, year = {2023}, institution = {Institute for Social Research, University of Michigan}, address = {Ann Arbor, MI}, abstract = {This document describes the collection of lnterleukin-6 (IL-6) in 2014 and 2016 Assays from Dried Blood Spots. }, keywords = {User guide}, author = {Crimmins, Eileen and Jessica Faul and Jung K Kim and David R Weir} } @article {12923, title = {Epigenetic-based age acceleration in a representative sample of older Americans: Associations with aging-related morbidity and mortality.}, journal = {PNAS}, volume = {120}, year = {2023}, pages = {e2215840120}, abstract = {

Biomarkers developed from DNA methylation (DNAm) data are of growing interest as predictors of health outcomes and mortality in older populations. However, it is unknown how epigenetic aging fits within the context of known socioeconomic and behavioral associations with aging-related health outcomes in a large, population-based, and diverse sample. This study uses data from a representative, panel study of US older adults to examine the relationship between DNAm-based age acceleration measures in the prediction of cross-sectional and longitudinal health outcomes and mortality. We examine whether recent improvements to these scores, using principal component (PC)-based measures designed to remove some of the technical noise and unreliability in measurement, improve the predictive capability of these measures. We also examine how well DNAm-based measures perform against well-known predictors of health outcomes such as demographics, SES, and health behaviors. In our sample, age acceleration calculated using "second and third generation clocks," PhenoAge, GrimAge, and DunedinPACE, is consistently a significant predictor of health outcomes including cross-sectional cognitive dysfunction, functional limitations and chronic conditions assessed 2 y after DNAm measurement, and 4-y mortality. PC-based epigenetic age acceleration measures do not significantly change the relationship of DNAm-based age acceleration measures to health outcomes or mortality compared to earlier versions of these measures. While the usefulness of DNAm-based age acceleration as a predictor of later life health outcomes is quite clear, other factors such as demographics, SES, mental health, and health behaviors remain equally, if not more robust, predictors of later life outcomes.

}, keywords = {Acceleration, Aging, Biomarkers, Cross-Sectional Studies, DNA Methylation, Epigenesis, genetic}, issn = {1091-6490}, doi = {10.1073/pnas.2215840120}, author = {Jessica Faul and Jung K Kim and Levine, Morgan E and Bharat Thyagarajan and David R Weir and Eileen M. Crimmins} } @article {13533, title = {Memory and language cognitive data harmonization across the United States and Mexico.}, journal = {Alzheimer{\textquoteright}s \& Dementia (Amsterdam, Netherlands)}, volume = {15}, year = {2023}, pages = {e12478}, abstract = {

INTRODUCTION: We used cultural neuropsychology-informed procedures to derive and validate harmonized scores representing memory and language across population-based studies in the United States and Mexico.

METHODS: Data were from the Health and Retirement Study Harmonized Cognitive Assessment Protocol (HRS-HCAP) and the Mexican Health and Aging Study (MHAS) Ancillary Study on Cognitive Aging (Mex-Cog). We statistically co-calibrated memory and language domains and performed differential item functioning (DIF) analysis using a cultural neuropsychological approach. We examined relationships among harmonized scores, age, and education.

RESULTS: We included 3170 participants from the HRS-HCAP (age~=~76.6 [standard deviation (SD): 7.5], 60\% female) and 2042 participants from the Mex-Cog (age~=~68.1 [SD: 9.0], 59\% female). Five of seven memory items and one of twelve language items demonstrated DIF by study. Harmonized memory and language scores showed expected associations with age and education.

DISCUSSION: A cultural neuropsychological approach to harmonization facilitates the generation of harmonized measures of memory and language function in cross-national studies.

HIGHLIGHTS: We harmonized memory and language scores across studies in the United States and Mexico.A cultural neuropsychological approach to data harmonization was used.Harmonized scores showed minimal measurement differences between cohorts.Future work can use these harmonized scores for cross-national studies of Alzheimer{\textquoteright}s disease and related dementias.

}, keywords = {Alzheimer{\textquoteright}s disease, cognitive aging, cross-cultural, cultural neuropsychology, harmonization}, issn = {2352-8729}, doi = {10.1002/dad2.12478}, author = {Arce Renter{\'\i}a, Miguel and Brice{\~n}o, Emily M and Chen, Diefei and Saenz, Joseph and Lindsay C Kobayashi and Gonzalez, Christopher and Vonk, Jet M J and Richard N Jones and Jennifer J Manly and Wong, Rebeca and David R Weir and Kenneth M. Langa and Gross, Alden L} } @article {13331, title = {The mode effect of web-based surveying on the 2018 HRS measure of cognitive functioning.}, journal = {J Gerontol B Psychol Sci Soc Sci}, year = {2023}, abstract = {

OBJECTIVES: Measuring cognition in an aging population is a public health priority. A move towards survey measurement via the web (as opposed to phone or in-person) is cost effective but challenging as it may induce bias in cognitive measures. We examine this possibility using an experiment embedded in the 2018 wave of data collection for the US Health and Retirement Study (HRS).

METHODS: We utilize techniques from multiple group item response theory to assess the effect of survey mode on performance on the HRS cognitive measure. We also study the problem of attrition by attempting to predict dropout and via approaches meant to minimize bias in subsequent inferences due to attrition.

RESULTS: We find evidence of an increase in scores for HRS respondents who are randomly assigned to the web-based mode of data collection in 2018. Web-based respondents score higher in 2018 than do phone-based respondents, and they show much larger gains relative to 2016 performance and subsequently larger declines in 2020. The bias in favor of web-based responding is observed across all items, but most pronounced for the serial 7 task and numeracy items. Due to the relative ease of the web-based mode, we suggest a cutscore of 12 being used to indicate CIND (cognitively impaired but not demented) status when using the web-based version rather than 11.

DISCUSSION: The difference in mode may be non-ignorable for many uses of the HRS cognitive measure. In particular, it may require reconsideration of some cutscore-based approaches to identify impairment.

}, issn = {1758-5368}, doi = {10.1093/geronb/gbad068}, author = {Domingue, Benjamin W and McCammon, Ryan and Brady T. West and Kenneth M. Langa and David R Weir and Jessica Faul} } @article {12903, title = {Psychosocial and Lifestyle Questionnaire 2006 - 2022}, year = {2023}, institution = {Survey Research Center, Institute for Social Research, University of Michigan}, address = {Ann Arbor, MI}, author = {Jacqui Smith and Lindsay H Ryan and Larkina, Marina and Amanda Sonnega and David R Weir} } @article {13225, title = {Representativeness of the oversamples of Blacks and Hispanics in the Health and Retirement Study: A geographic analysis of 2020}, year = {2023}, institution = {Survey Research Center, Institute for Social Research, University of Michigan}, address = {Ann Arbor, MI}, keywords = {Methodology, minorities, oversampling, survey design}, author = {Schroeder, Heather and David R Weir and Brady T. West} } @article {11926, title = {Age-related differences in T cell subsets in a nationally representative sample of people over age 55: Findings from the Health and Retirement Study.}, journal = {The Journals of Gerontology, Series A }, volume = {77}, year = {2022}, pages = {927-933}, abstract = {

Though T cell immunosenescence is a major risk factor for age-related diseases, susceptibility to infections, and responses to vaccines, differences in T cells subset counts and representation by age and sex have not been determined for a large sample representative of the national population of the US. We evaluated the counts of T cell subsets including total, CD4+ and CD8+ T cells, and their na{\"\i}ve (Tn), effector memory (Tem) and effector subsets, in the context of age, sex and exposure to cytomegalovirus (CMV) infection among 8,848 Health and Retirement Study (HRS) participants, a nationally representative study of adults over 55 years. Total T cells (CD3+) and CD4+ cells declined markedly with age; CD8+ T cells declined somewhat less. While CD4+ T cell declines with age occurred for both CMV seropositive and CMV seronegative groups, total T cells and CD8+ cells were both substantially higher among the CMV seropositive group. Numbers of Tn CD4+ and CD8+ cells were strongly and inversely related to age, were better conserved among women, and were independent of CMV seropositivity. By contrast, accumulation of the CD8+ and CD4+ Tem and effector subsets was CMV-associated. This is the first study to provide counts of T cell subsets by age and sex in a national sample of older US adults over the age of 55 years. Understanding T cell changes with age and sex is an important first step in determining strategies to reduce its impact on age-related diseases and susceptibility to infection.

}, keywords = {Aging, CMV Seropositivity}, issn = {1758-535X}, doi = {10.1093/gerona/glab300}, author = {Bharat Thyagarajan and Jessica Faul and Vivek, Sithara and Jung K Kim and Nikolich-{\v Z}ugich, Janko and David R Weir and Eileen M. Crimmins} } @article {10.1001/jamaneurol.2022.3543, title = {Estimating the Prevalence of Dementia and Mild Cognitive Impairment in the US: The 2016 Health and Retirement Study Harmonized Cognitive Assessment Protocol Project}, journal = {JAMA Neurology}, volume = {79}, year = {2022}, pages = {1242-1249}, abstract = {Nationally representative data are critical for understanding the causes, costs, and outcomes associated with dementia and mild cognitive impairment (MCI) in the US and can inform policies aimed at reducing the impact of these conditions on patients, families, and public programs. The nationally representative Health and Retirement Study (HRS) is an essential resource for such data, but the HRS substudy providing dementia diagnostic information was fielded more than 20 years ago and more recent data are needed.The Harmonized Cognitive Assessment Protocol (HCAP) was developed to update national estimates of the prevalence of MCI and dementia in the US and examine differences by age, race, ethnicity, and sex.HRS is an ongoing longitudinal nationally representative study of people 51 years and older with staggered entry dates from 1992 to 2022 and follow-up ranging from 4 to 30 years. HCAP is a cross-sectional random sample of individuals in HRS who were 65 years or older in 2016. Of 9972 age-eligible HRS participants, 4425 were randomly selected for HCAP, and 3496 completed a comprehensive neuropsychological test battery and informant interview, none of whom were excluded. Dementia and MCI were classified using an algorithm based on standard diagnostic criteria and comparing test performance to a robust normative sample.Groups were stratified by age, sex, education, race, and ethnicity.National prevalence estimates using population weights.The mean (SD) age of the study population sample (N = 3496) was 76.4 (7.6) years, and 2095 participants (60\%) were female. There were 551 participants who self-identified as Black and not Hispanic (16\%), 382 who self-identified as Hispanic regardless of race (16\%), 2483 who self-identified as White and not Hispanic (71\%), and 80 who self-identified as another race (2\%), including American Indian or Alaska Native, Asian, Native Hawaiian or Pacific Islander, or another self-described race. A total of 393 individuals (10\%; 95\% CI, 9-11) were classified as having dementia and 804 (22\%; 95\% CI, 20-24) as having MCI. Every 5-year increase in age was associated with higher risk of dementia (weighted odds ratio [OR], 1.95 per 5-year age difference; 95\%, CI, 1.77-2.14) and MCI (OR, 1.17 per 5-year age difference, 95\% CI, 1.09-1.26). Each additional year of education was associated with a decrease in risk of dementia (OR, 0.93 per year of school, 95\% CI, 0.89-0.97) and MCI (OR, 0.94, 95\% CI, 0.91-0.97). Dementia was more common among non-Hispanic Black individuals (OR, 1.81; 95\% CI, 1.20-2.75) and MCI in Hispanic individuals (OR, 1.42; 95\% CI, 1.03-1.96) compared with non-Hispanic White individuals. Other group comparisons by race and ethnicity were not possible owing to small numbers. No differences in prevalence were found between female individuals and male individuals.Using a comprehensive neuropsychological test battery and large sample, the national prevalence of dementia and MCI in 2016 found in this cross-sectional study was similar to that of other US-based studies, indicating a disproportionate burden of dementia and MCI among older Black and Hispanic adults and those with lower education.}, keywords = {Dementia, HCAP, mild cognitive impairment}, issn = {2168-6149}, doi = {10.1001/jamaneurol.2022.3543}, author = {Jennifer J Manly and Richard N Jones and Kenneth M. Langa and Ryan, Lindsay H. and Levine, Deborah A. and McCammon, Ryan and Heeringa, Steven G. and David R Weir} } @article {13496, title = {Exome Array Analysis of 9721 Ischemic Stroke Cases from the SiGN Consortium.}, journal = {Genes }, volume = {14}, year = {2022}, pages = {61}, abstract = {

Recent genome wide association studies have identified 89 common genetic variants robustly associated with ischemic stroke and primarily located in non-coding regions. To evaluate the contribution of coding variants, which are mostly rare, we performed an exome array analysis on 106,101 SNPs for 9721 ischemic stroke cases from the SiGN Consortium, and 12,345 subjects with no history of stroke from the Health Retirement Study and SiGN consortium. We identified 15 coding variants significantly associated with all ischemic stroke at array-wide threshold (i.e., < 4.7 {\texttimes} 10), including two common SNPs in that have previously been associated with stroke. Twelve of the remaining 13 variants were extremely rare in European Caucasians (MAF < 0.1\%) and the associations were driven by African American samples. There was no evidence for replication of these associations in either TOPMed Stroke samples ( = 5613 cases) or UK Biobank ( = 5874 stroke cases), although power to replicate was very low given the low allele frequencies of the associated variants and a shortage of samples from diverse ancestries. Our study highlights the need for acquiring large, well-powered diverse cohorts to study rare variants, and the technical challenges using array-based genotyping technologies for rare variant genotyping.

}, keywords = {Exome, Gene Frequency, Genome-Wide Association Study, Ischemic stroke, Stroke}, issn = {2073-4425}, doi = {10.3390/genes14010061}, author = {Xu, Huichun and Nguyen, Kevin and Gaynor, Brady J and Ling, Hua and Zhao, Wei and McArdle, Patrick F and O{\textquoteright}Connor, Timothy D and Stine, O Colin and Ryan, Kathleen A and Lynch, Megan and Smith, Jennifer A and Jessica Faul and Hu, Yao and Haessler, Jeffrey W and Fornage, Myriam and Kooperberg, Charles and Perry, James A and Hong, Charles C and Cole, John W and Pugh, Elizabeth and Doheny, Kimberly and Sharon L R Kardia and David R Weir and Kittner, Steven J and Mitchell, Braxton D} } @article {12707, title = {Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning.}, journal = {Molecular Psychiatry}, year = {2022}, abstract = {

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.

}, keywords = {Genome, health outcomes, Memory, neurocognitive outcomes, polygenic score, Verbal Learning}, issn = {1476-5578}, doi = {10.1038/s41380-022-01710-8}, author = {Lahti, Jari and Tuominen, Samuli and Yang, Qiong and Pergola, Giulio and Ahmad, Shahzad and Amin, Najaf and Armstrong, Nicola J and Beiser, Alexa and Bey, Katharina and Bis, Joshua C and Boerwinkle, Eric and Bressler, Jan and Campbell, Archie and Campbell, Harry and Chen, Qiang and Corley, Janie and Cox, Simon R and Davies, Gail and De Jager, Philip L and Derks, Eske M and Jessica Faul and Fitzpatrick, Annette L and Fohner, Alison E and Ford, Ian and Fornage, Myriam and Gerring, Zachary and Grabe, Hans J and Grodstein, Francine and Gudnason, Vilmundur and Simonsick, Eleanor and Holliday, Elizabeth G and Joshi, Peter K and Kajantie, Eero and Kaprio, Jaakko and Karell, Pauliina and Kleineidam, Luca and Knol, Maria J and Kochan, Nicole A and Kwok, John B and Leber, Markus and Lam, Max and Lee, Teresa and Li, Shuo and Loukola, Anu and Luck, Tobias and Marioni, Riccardo E and Mather, Karen A and Medland, Sarah and Mirza, Saira S and Nalls, Mike A and Nho, Kwangsik and O{\textquoteright}Donnell, Adrienne and Oldmeadow, Christopher and Painter, Jodie and Pattie, Alison and Reppermund, Simone and Risacher, Shannon L and Rose, Richard J and Sadashivaiah, Vijay and Scholz, Markus and Satizabal, Claudia L and Schofield, Peter W and Schraut, Katharina E and Scott, Rodney J and Simino, Jeannette and Smith, Albert V and Smith, Jennifer A and Stott, David J and Surakka, Ida and Teumer, Alexander and Thalamuthu, Anbupalam and Trompet, Stella and Turner, Stephen T and van der Lee, Sven J and Villringer, Arno and V{\"o}lker, Uwe and Wilson, Robert S and Wittfeld, Katharina and Vuoksimaa, Eero and Xia, Rui and Yaffe, Kristine and Yu, Lei and Zare, Habil and Zhao, Wei and Ames, David and Attia, John and Bennett, David A and Brodaty, Henry and Chasman, Daniel I and Goldman, Aaron L and Hayward, Caroline and Ikram, M Arfan and Jukema, J Wouter and Sharon L R Kardia and Lencz, Todd and Loeffler, Markus and Mattay, Venkata S and Palotie, Aarno and Psaty, Bruce M and Ramirez, Alfredo and Ridker, Paul M and Riedel-Heller, Steffi G and Sachdev, Perminder S and Saykin, Andrew J and Scherer, Martin and Schofield, Peter R and Sidney, Stephen and Starr, John M and Trollor, Julian and Ulrich, William and Wagner, Michael and David R Weir and Wilson, James F and Wright, Margaret J and Weinberger, Daniel R and Debette, St{\'e}phanie and Eriksson, Johan G and Mosley, Thomas H and Launer, Lenore J and van Duijn, Cornelia M and Deary, Ian J and Seshadri, Sudha and R{\"a}ikk{\"o}nen, Katri} } @article {5760, title = {Health and Retirement Study Imputation of Cognitive Functioning Measures: 1992-2018}, year = {2022}, institution = {Survey Research Center, University of Michigan}, address = {Ann Arbor, Michigan}, keywords = {Health Conditions and Status, Methodology}, url = {https://hrsdata.isr.umich.edu/sites/default/files/documentation/data-descriptions/1651088507/COGIMP9218_dd.pdf}, author = {Ryan J McCammon and Gwenith G Fisher and Hassan, Halimah and Jessica Faul and Rogers, Willard and David R Weir} } @article {12749, title = {LHMS User Guide 2015-2017}, year = {2022}, institution = {Institute for Social Research, University of Michigan }, address = {Ann Arbor, MI}, keywords = {life history, mail survey, User guide}, author = {Jacqui Smith and Ofstedal, Mary Beth and Larkina, Marina and Helppie-McFall, Brooke and Amanda Sonnega and David R Weir} } @article {12989, title = {MODE EFFECTS ON COGNITIVE FUNCTIONING ASSESSMENTS IN THE HEALTH AND RETIREMENT STUDY}, journal = {Innovation in Aging}, volume = {6}, year = {2022}, pages = {163}, abstract = {As the population of the US ages, there is interest in assessing health conditions associated with age and longevity, such as age-related decline in cognitive functioning. As a result, there is an increased focus on measuring cognitive functioning in surveys of older populations. One challenge relates to conducting comparable measurement across survey modes (e.g., phone vs. web). Compounding this is that mode of survey administration is often not assigned randomly making inter-group comparison more difficult. This paper addresses these issues using a novel experiment embedded within the Health and Retirement Study (HRS). The HRS, a US-based cohort of people over 50, has measured cognition since its inception using both in-person and telephone modes. In 2018, a sample of approximately 3700 respondents was identified as web-eligible based on a prior report of internet access along with other selection criteria. Of these, 60\% were randomly selected for the web sample with the remainder serving as controls, assigned to telephone mode for comparison purposes. We deploy techniques from item response theory (IRT) and differential item functioning (DIF) to estimate the difference in cognitive functioning between web and phone respondents in 2018 based on longitudinal cognition data collected prior to 2018. Second, we estimate the overall effect of taking the survey via the web as compared to the phone. Third, we examine item-level variation in the magnitude of the mode effect and suggest possible methods for adjustment to support longitudinal consistency. These results are important in guiding future research that utilizes web-based cognitive measures.}, keywords = {Cognition, cognitive functioning assessments}, doi = {10.1093/geroni/igac059.652}, author = {Jessica Faul and Domingue, Ben and Stenhaug, Ben and Brady T. West and Kenneth M. Langa and David R Weir} } @conference {11803, title = {Assessing the Economic Impact Payment in the Older Population}, booktitle = {Retirement and Disability Research Consortium 23rd Annual Meeting}, year = {2021}, month = {08/2021}, publisher = {Center for Financial Security, University of Wisconsin-Madison}, organization = {Center for Financial Security, University of Wisconsin-Madison}, address = {Virtual Event}, abstract = {The COVID-19 pandemic is the greatest threat to the health and well-being of the older population in at least a century. The economic consequences of public health policies to mitigate that threat are also of serious concern. This project proposes to study one part of the policy response. We will use data collected by the Health and Retirement Study in its 2020 wave to study awareness and impact of the Economic Impact Payment (EIP) stimulus on different groups of older Americans during the coronavirus pandemic. The EIP was authorized as part of the Coronavirus Aid, Relief, and Economic Security (CARES) Act passed in late March 2020. It provides for a direct stimulus payment to individuals, similar to stimulus programs in previous economic downturns in 2001 and 2008. The great advantage to studying the impact of the EIP in HRS is the volume of other information that can be used to understand differentials in eligibility, awareness, and disposition. From the 2020 survey we will know about the impact of COVID-19 on work and health, as well as the usual measures of income and wealth. }, keywords = {COVID-19, economic impact, Stimulus effects}, url = {https://cfsrdrc.wisc.edu/files/2021-RDRC-Meeting-Booklet.pdf$\#$page=7}, author = {Kezdi, Gabor and David R Weir} } @article {11384, title = {Associations of Age, Sex, Race/Ethnicity and Education with 13 Epigenetic Clocks in a Nationally Representative US Sample: The Health and Retirement Study.}, journal = {The Journals of Gerontology: Series A }, volume = {76}, year = {2021}, pages = {1117-1123}, abstract = {

BACKGROUND: Many DNA methylation based indicators have been developed as summary measures of epigenetic aging. We examine the associations between 13 epigenetic clocks, including 4 second generation clocks, as well as the links of the clocks to social, demographic and behavioral factors known to be related to health outcomes: sex, race/ethnicity, socioeconomic status, obesity and lifetime smoking pack years.

METHODS: The Health and Retirement Study is the data source which is a nationally representative sample of Americans over age 50. Assessment of DNA methylation was based on the EPIC chip and epigenetic clocks were developed based on existing literature.

RESULTS: The clocks vary in the strength of their relationships with age, with each other and with independent variables. Second generation clocks trained on health related characteristics tend to relate more strongly to the sociodemographic and health behaviors known to be associated with health outcomes in this age group.

CONCLUSIONS: Users of this publicly available data set should be aware that epigenetic clocks vary in their relationships to age and to variables known to be related to the process of health change with age.

}, keywords = {DNA Methylation, DunedinPoAm38, Epigenetic Age, GrimAge, PhenoAgeAcceleration}, issn = {1758-535X}, doi = {10.1093/gerona/glab016}, author = {Eileen M. Crimmins and Bharat Thyagarajan and Morgan E. Levine and David R Weir and Jessica Faul} } @article {12121, title = {Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.}, journal = {The American Journal of Human Genetics}, volume = {108}, year = {2021}, pages = {564-582}, abstract = {

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5\%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained <=20 variants in the credible sets that jointly account for 99\% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.

}, keywords = {Africa, African Americans, Blacks, Body Height, Europe, Female, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2021.02.011}, author = {Graff, Mariaelisa and Justice, Anne E and Young, Kristin L and Marouli, Eirini and Zhang, Xinruo and Fine, Rebecca S and Lim, Elise and Buchanan, Victoria and Rand, Kristin and Feitosa, Mary F and Wojczynski, Mary K and Yanek, Lisa R and Shao, Yaming and Rohde, Rebecca and Adeyemo, Adebowale A and Aldrich, Melinda C and Matthew A. Allison and Ambrosone, Christine B and Ambs, Stefan and Amos, Christopher and Donna K Arnett and Atwood, Larry and Bandera, Elisa V and Traci M Bartz and Becker, Diane M and Berndt, Sonja I and Bernstein, Leslie and Bielak, Lawrence F and Blot, William J and Erwin P Bottinger and Bowden, Donald W and Bradfield, Jonathan P and Brody, Jennifer A and Broeckel, Ulrich and Burke, Gregory and Brian E Cade and Cai, Qiuyin and Caporaso, Neil and Carlson, Chris and John Carpten and Casey, Graham and Chanock, Stephen J and Chen, Guanjie and Chen, Minhui and Chen, Yii-Der I and Chen, Wei-Min and Chesi, Alessandra and Chiang, Charleston W K and Chu, Lisa and Coetzee, Gerry A and Conti, David V and Cooper, Richard S and Cushman, Mary and Ellen W Demerath and Deming, Sandra L and Dimitrov, Latchezar and Ding, Jingzhong and Diver, W Ryan and Duan, Qing and Michele K Evans and Falusi, Adeyinka G and Jessica Faul and Myriam Fornage and Caroline S Fox and Freedman, Barry I and Garcia, Melissa and Gillanders, Elizabeth M and Phyllis J Goodman and Gottesman, Omri and Grant, Struan F A and Guo, Xiuqing and Hakonarson, Hakon and Haritunians, Talin and Tamara B Harris and Harris, Curtis C and Henderson, Brian E and Hennis, Anselm and Dena G Hernandez and Hirschhorn, Joel N and McNeill, Lorna Haughton and Howard, Timothy D and Howard, Barbara and Hsing, Ann W and Hsu, Yu-Han H and Hu, Jennifer J and Huff, Chad D and Huo, Dezheng and Ingles, Sue A and Irvin, Marguerite R and John, Esther M and Johnson, Karen C and Jordan, Joanne M and Kabagambe, Edmond K and Kang, Sun J and Sharon L R Kardia and Keating, Brendan J and Rick A Kittles and Eric A Klein and Kolb, Suzanne and Kolonel, Laurence N and Charles Kooperberg and Kuller, Lewis and Kutlar, Abdullah and Leslie A Lange and Langefeld, Carl D and Loic Le Marchand and Leonard, Hampton and Lettre, Guillaume and Levin, Albert M and Li, Yun and Li, Jin and Liu, Yongmei and Liu, Youfang and Liu, Simin and Kurt Lohman and Lotay, Vaneet and Lu, Yingchang and Maixner, William and JoAnn E Manson and McKnight, Barbara and Meng, Yan and Monda, Keri L and Monroe, Kris and Moore, Jason H and Thomas H Mosley and Mudgal, Poorva and Murphy, Adam B and Nadukuru, Rajiv and Michael A Nalls and Nathanson, Katherine L and Nayak, Uma and N{\textquoteright}Diaye, Amidou and Nemesure, Barbara and Neslund-Dudas, Christine and Neuhouser, Marian L and Nyante, Sarah and Ochs-Balcom, Heather and Ogundiran, Temidayo O and Ogunniyi, Adesola and Ojengbede, Oladosu and Okut, Hayrettin and Olopade, Olufunmilayo I and Olshan, Andrew and Padhukasahasram, Badri and Palmer, Julie and Palmer, Cameron D and Palmer, Nicholette D and George J Papanicolaou and Patel, Sanjay R and Pettaway, Curtis A and Peyser, Patricia A and Press, Michael F and Rao, D C and Rasmussen-Torvik, Laura J and Redline, Susan and Reiner, Alex P and Rhie, Suhn K and Rodriguez-Gil, Jorge L and Charles N Rotimi and Rotter, Jerome I and Ruiz-Narvaez, Edward A and Rybicki, Benjamin A and Babatunde Salako and Sale, Michele M and Sanderson, Maureen and Eric E Schadt and Schreiner, Pamela J and Schurmann, Claudia and Schwartz, Ann G and Daniel Shriner and Signorello, Lisa B and Andrew B Singleton and David S Siscovick and Smith, Jennifer A and Smith, Shad and Elizabeth K Speliotes and Spitz, Margaret and Stanford, Janet L and Stevens, Victoria L and Stram, Alex and Strom, Sara S and Sucheston, Lara and Yan V Sun and Tajuddin, Salman M and Taylor, Herman and Taylor, Kira and Bamidele O Tayo and Michael J Thun and Tucker, Margaret A and Vaidya, Dhananjay and Van Den Berg, David J and Vedantam, Sailaja and Vitolins, Mara and Wang, Zhaoming and Erin B Ware and Wassertheil-Smoller, Sylvia and David R Weir and Wiencke, John K and Williams, Scott M and L Keoki Williams and Wilson, James G and Witte, John S and Wrensch, Margaret and Wu, Xifeng and Yao, Jie and Zakai, Neil and Zanetti, Krista and Zemel, Babette S and Zhao, Wei and Jing Hua Zhao and Zheng, Wei and Zhi, Degui and Zhou, Jie and Zhu, Xiaofeng and Ziegler, Regina G and Zmuda, Joe and Alan B Zonderman and Psaty, Bruce M and Ingrid B Borecki and Cupples, L Adrienne and Liu, Ching-Ti and Christopher A Haiman and Ruth J F Loos and Ng, Maggie C Y and Kari E North} } @article {12127, title = {Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.}, journal = {Mol Psychiatry}, volume = {26}, year = {2021}, pages = {2111-2125}, abstract = {

Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 {\texttimes} 10). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.

}, keywords = {Blood pressure, Epistasis, Genetic, Genetic Loci, Genome-Wide Association Study, Humans, Hypertension, Polymorphism, Single Nucleotide}, issn = {1476-5578}, doi = {10.1038/s41380-020-0719-3}, author = {de Las Fuentes, Lisa and Yun Ju Sung and Noordam, Raymond and Thomas W Winkler and Feitosa, Mary F and Schwander, Karen and Bentley, Amy R and Brown, Michael R and Guo, Xiuqing and Alisa Manning and Daniel I Chasman and Aschard, Hugues and Traci M Bartz and Bielak, Lawrence F and Campbell, Archie and Cheng, Ching-Yu and Dorajoo, Rajkumar and Hartwig, Fernando P and Horimoto, A R V R and Li, Changwei and Li-Gao, Ruifang and Liu, Yongmei and Marten, Jonathan and Musani, Solomon K and Ntalla, Ioanna and Rankinen, Tuomo and Melissa Richard and Sim, Xueling and Smith, Albert V and Tajuddin, Salman M and Bamidele O Tayo and Vojinovic, Dina and Warren, Helen R and Xuan, Deng and Alver, Maris and Boissel, Mathilde and Jin-Fang Chai and Chen, Xu and Christensen, Kaare and Divers, Jasmin and Evangelou, Evangelos and Gao, Chuan and Giorgia G Girotto and Sarah E Harris and He, Meian and Hsu, Fang-Chi and K{\"u}hnel, Brigitte and Laguzzi, Federica and Li, Xiaoyin and Lyytik{\"a}inen, Leo-Pekka and Ilja M Nolte and Poveda, Alaitz and Rauramaa, Rainer and Riaz, Muhammad and Rueedi, Rico and Shu, Xiao-Ou and Snieder, Harold and Sofer, Tamar and Takeuchi, Fumihiko and Verweij, Niek and Erin B Ware and Weiss, Stefan and Yanek, Lisa R and Amin, Najaf and Dan E Arking and Donna K Arnett and Bergmann, Sven and Boerwinkle, Eric and Brody, Jennifer A and Broeckel, Ulrich and Brumat, Marco and Burke, Gregory and Cabrera, Claudia P and Canouil, Micka{\"e}l and Chee, Miao Li and Chen, Yii-Der Ida and Cocca, Massimiliano and Connell, John and de Silva, H Janaka and de Vries, Paul S and Eiriksdottir, Gudny and Jessica Faul and Fisher, Virginia and Forrester, Terrence and Fox, Ervin F and Friedlander, Yechiel and Gao, He and Gigante, Bruna and Giulianini, Franco and Gu, Chi Charles and Gu, Dongfeng and Tamara B Harris and He, Jiang and Heikkinen, Sami and Heng, Chew-Kiat and Hunt, Steven and Ikram, M Arfan and Irvin, Marguerite R and K{\"a}h{\"o}nen, Mika and Kavousi, Maryam and Khor, Chiea Chuen and Kilpel{\"a}inen, Tuomas O and Koh, Woon-Puay and Komulainen, Pirjo and Kraja, Aldi T and Krieger, J E and Langefeld, Carl D and Li, Yize and Liang, Jingjing and David C Liewald and Liu, Ching-Ti and Liu, Jianjun and Kurt Lohman and M{\"a}gi, Reedik and McKenzie, Colin A and Meitinger, Thomas and Andres Metspalu and Milaneschi, Yuri and Lili Milani and Dennis O Mook-Kanamori and Michael A Nalls and Nelson, Christopher P and Norris, Jill M and Jeff O{\textquoteright}Connell and Ogunniyi, Adesola and Padmanabhan, Sandosh and Palmer, Nicholette D and Nancy L Pedersen and Thomas T Perls and Peters, Annette and Petersmann, Astrid and Peyser, Patricia A and Polasek, Ozren and David J Porteous and Raffel, Leslie J and Rice, Treva K and Rotter, Jerome I and Rudan, Igor and Rueda-Ochoa, Oscar-Leonel and Sabanayagam, Charumathi and Babatunde Salako and Schreiner, Pamela J and Shikany, James M and Stephen Sidney and Sims, Mario and Sitlani, Colleen M and Smith, Jennifer A and John M Starr and Strauch, Konstantin and Swertz, Morris A and Teumer, Alexander and Tham, Yih Chung and Andr{\'e} G Uitterlinden and Vaidya, Dhananjay and van der Ende, M Yldau and Waldenberger, Melanie and Wang, Lihua and Wang, Ya-Xing and Wei, Wen-Bin and David R Weir and Wen, Wanqing and Yao, Jie and Yu, Bing and Yu, Caizheng and Yuan, Jian-Min and Zhao, Wei and Alan B Zonderman and Becker, Diane M and Bowden, Donald W and Ian J Deary and D{\"o}rr, Marcus and T{\~o}nu Esko and Freedman, Barry I and Froguel, Philippe and Paolo P. Gasparini and Gieger, Christian and Jost Bruno Jonas and Kammerer, Candace M and Kato, Norihiro and Lakka, Timo A and Leander, Karin and Lehtim{\"a}ki, Terho and Patrik K E Magnusson and Marques-Vidal, Pedro and Brenda W J H Penninx and Nilesh J Samani and van der Harst, Pim and Wagenknecht, Lynne E and Wu, Tangchun and Zheng, Wei and Zhu, Xiaofeng and Bouchard, Claude and Cooper, Richard S and Correa, Adolfo and Michele K Evans and Gudnason, Vilmundur and Caroline Hayward and Horta, Bernardo L and Tanika N Kelly and Stephen B Kritchevsky and Levy, Daniel and Walter R Palmas and Pereira, A C and Province, Michael M and Psaty, Bruce M and Ridker, Paul M and Charles N Rotimi and Tai, E Shyong and van Dam, Rob M and Cornelia M van Duijn and Wong, Tien Yin and Kenneth Rice and Gauderman, W James and Alanna C Morrison and Kari E North and Sharon L R Kardia and Caulfield, Mark J and Elliott, Paul and Munroe, Patricia B and Franks, Paul W and Rao, Dabeeru C and Myriam Fornage} } @article {12126, title = {Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits.}, journal = {Human Genetics and Genomics Advances}, volume = {2}, year = {2021}, pages = {100013}, abstract = {

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from 5 ancestry groups. In the combined meta-analyses of Stages 1 and 2, we identified 59 loci (p value <5e-8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (), synaptic function and neurotransmission (), as well as genes previously implicated in neuropsychiatric or stress-related disorders (). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.

}, keywords = {blood pressure traits}, issn = {2666-2477}, doi = {10.1016/j.xhgg.2020.100013}, author = {Sun, Daokun and Melissa Richard and Musani, Solomon K and Yun Ju Sung and Thomas W Winkler and Schwander, Karen and Jin-Fang Chai and Guo, Xiuqing and Kilpel{\"a}inen, Tuomas O and Vojinovic, Dina and Aschard, Hugues and Traci M Bartz and Bielak, Lawrence F and Brown, Michael R and Chitrala, Kumaraswamy and Hartwig, Fernando P and Horimoto, Andrea R V R and Liu, Yongmei and Alisa Manning and Noordam, Raymond and Smith, Albert V and Sarah E Harris and K{\"u}hnel, Brigitte and Lyytik{\"a}inen, Leo-Pekka and Ilja M Nolte and Rauramaa, Rainer and van der Most, Peter J and Wang, Rujia and Erin B Ware and Weiss, Stefan and Wen, Wanqing and Yanek, Lisa R and Dan E Arking and Donna K Arnett and Barac, Ana and Boerwinkle, Eric and Broeckel, Ulrich and Chakravarti, Aravinda and Chen, Yii-Der Ida and Cupples, L Adrienne and Davigulus, Martha L and de Las Fuentes, Lisa and de Mutsert, Ren{\'e}e and de Vries, Paul S and Delaney, Joseph A C and Ana V Diez Roux and D{\"o}rr, Marcus and Jessica Faul and Fretts, Amanda M and Gallo, Linda C and Hans-J{\"o}rgen Grabe and Gu, C Charles and Tamara B Harris and Hartman, Catharina C A and Heikkinen, Sami and Ikram, M Arfan and Isasi, Carmen and Johnson, W Craig and Jost Bruno Jonas and Kaplan, Robert C and Komulainen, Pirjo and Krieger, Jose E and Levy, Daniel and Liu, Jianjun and Kurt Lohman and Luik, Annemarie I and Martin, Lisa W and Meitinger, Thomas and Milaneschi, Yuri and Jeff O{\textquoteright}Connell and Walter R Palmas and Peters, Annette and Peyser, Patricia A and Pulkki-Raback, Laura and Raffel, Leslie J and Reiner, Alex P and Kenneth Rice and Robinson, Jennifer G and Rosendaal, Frits R and Schmidt, Carsten Oliver and Schreiner, Pamela J and Schwettmann, Lars and Shikany, James M and Shu, Xiao-Ou and Stephen Sidney and Sims, Mario and Smith, Jennifer A and Sotoodehnia, Nona and Strauch, Konstantin and Tai, E Shyong and Taylor, Kent and Andr{\'e} G Uitterlinden and Cornelia M van Duijn and Waldenberger, Melanie and Wee, Hwee-Lin and Wei, Wen-Bin and Wilson, Gregory and Xuan, Deng and Yao, Jie and Zeng, Donglin and Zhao, Wei and Zhu, Xiaofeng and Alan B Zonderman and Becker, Diane M and Ian J Deary and Gieger, Christian and Lakka, Timo A and Lehtim{\"a}ki, Terho and Kari E North and Oldehinkel, Albertine J and Brenda W J H Penninx and Snieder, Harold and Wang, Ya-Xing and David R Weir and Zheng, Wei and Michele K Evans and Gauderman, W James and Gudnason, Vilmundur and Horta, Bernardo L and Liu, Ching-Ti and Dennis O Mook-Kanamori and Alanna C Morrison and Pereira, Alexandre C and Psaty, Bruce M and Amin, Najaf and Fox, Ervin R and Charles Kooperberg and Sim, Xueling and Laura Bierut and Rotter, Jerome I and Sharon L R Kardia and Franceschini, Nora and Rao, Dabeeru C and Myriam Fornage} } @article {11422, title = {Quest for a summary measure of biological age: The Health and Retirement Study.}, journal = {Geroscience}, volume = {43}, year = {2021}, pages = {395-408}, abstract = {

Measures of biological age and its components have been shown to provide important information about individual health and prospective change in health as there is clear value in being able to assess whether someone is experiencing accelerated or decelerated aging. However, how to best assess biological age remains a question. We compare prediction of health outcomes using existing summary measures of biological age with a measure created by adding novel biomarkers related to aging to measures based on more conventional clinical chemistry and exam measures. We also compare the explanatory power of summary biological age measures compared to the individual biomarkers used to construct the measures. To accomplish this, we examine how well biological age, phenotypic age, and expanded biological age and five sets of individual biomarkers explain variability in four major health outcomes linked to aging in a large, nationally representative cohort of older Americans. We conclude that different summary measures of accelerated aging do better at explaining different health outcomes, and that chronological age has greater explanatory power for both cognitive dysfunction and mortality than the summary measures. In addition, we find that there is reduction in the variance explained in health outcomes when indicators are combined into summary measures, and that combining clinical indicators with more novel markers related to aging does best at explaining health outcomes. Finally, it is hard to define a set of assays that parsimoniously explains the greatest amount of variance across the range of health outcomes studied here. All of the individual markers considered were related to at least one of the health outcomes.

}, keywords = {Biological age, Biomarkers, Phenotypic age, TAME markers}, issn = {2509-2723}, doi = {10.1007/s11357-021-00325-1}, author = {Eileen M. Crimmins and Bharat Thyagarajan and Jung K Kim and David R Weir and Jessica Faul} } @article {11008, title = {Cognitive Function and Cardiometabolic-Inflammatory Risk Factors Among Older Indians and Americans.}, journal = {Journal of the American Geriatrics Society}, volume = {68 }, year = {2020}, pages = {S36-S44}, abstract = {

OBJECTIVES: To investigate how cardiometabolic-inflammatory risk factors are related to cognition among older adults in India and the United States.

DESIGN: The Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD) and the Harmonized Cognitive Assessment Protocol of the Health and Retirement Study (HRS-HCAP) in the United States conducted an in-depth assessment of cognition, using protocols designed for international comparison.

SETTING: Cognitive tests were conducted in hospital or household settings in India and in household settings in the United States.

PARTICIPANTS: Respondents aged 60 years and older from LASI-DAD (N = 1,865) and respondents aged 65 years and older from HRS-HCAP (N = 2,111) who provided venous blood specimen.

MEASUREMENTS: We used total composite scores from the common cognitive tests administered. Cardiovascular risk was indicated by systolic and diastolic blood pressure, pulse rate, pro-B-type natriuretic peptide (proBNP), and homocysteine. Metabolic risk was measured by body mass index, glycosylated hemoglobin (HbA1c), high-density lipoprotein cholesterol, and lipoprotein (a) (only in India). Inflammatory risk was indicted by white blood cell count, C-reactive protein, albumin, and uric acid (only in India).

RESULTS: The distribution of both total cognition scores and of cardiometabolic risk factors differed significantly between India and the United States. In both countries, lower cognition was associated with older age, lower education, elevated homocysteine, elevated proBNP, and lower albumin levels. The associations between HbA1c levels and cognitive measures were statistically significant in both countries, but in the opposite direction, with a coefficient of 1.5 (P < .001) in India and -2.4 (P < .001) in the United States for one percentage increase in absolute HbA1c value.

CONCLUSION: Cardiometabolic-inflammatory biomarkers are associated with cognitive functional levels in each country, but the relationships may vary across countries. J Am Geriatr Soc 68:S36-S44, 2020.

}, keywords = {cardiometabolic risk, Cognition, HCAP, LASI-DAD}, issn = {1532-5415}, doi = {10.1111/jgs.16734}, author = {Hu, Peifeng and Jinkook Lee and Beaumaster, Sidney and Jung K Kim and Dey, Sharmistha and David R Weir and Eileen M. Crimmins} } @article {12130, title = {Genome-wide association study of cognitive function in diverse Hispanics/Latinos: results from the Hispanic Community Health Study/Study of Latinos.}, journal = {Translational Psychiatry}, volume = {10}, year = {2020}, pages = {245}, abstract = {

Cognitive function such as reasoning, attention, memory, and language is strongly correlated with brain aging. Compared to non-Hispanic whites, Hispanics/Latinos have a higher risk of cognitive impairment and dementia. The genetic determinants of cognitive function have not been widely explored in this diverse and admixed population. We conducted a genome-wide association analysis of cognitive function in up to 7600 middle aged and older Hispanics/Latinos (mean = 55 years) from the Hispanic Community Health Study / Study of Latinos (HCHS/SOL). Four cognitive measures were examined: the Brief Spanish English Verbal Learning Test (B-SEVLT), the Word Fluency Test (WFT), the Digit Symbol Substitution Test (DSST), the Six-Item Screener (SIS). Four novel loci were identified: one for B-SEVLT at 4p14, two for WFT at 3p14.1 and 6p21.32, and one for DSST at 10p13. These loci implicate genes highly expressed in brain and previously connected to neurological diseases (UBE2K, FRMD4B, the HLA gene complex). By applying tissue-specific gene expression prediction models to our genotype data, additional genes highly expressed in brain showed suggestive associations with cognitive measures possibly indicating novel biological mechanisms, including IFT122 in the hippocampus for SIS, SNX31 in the basal ganglia for B-SEVLT, RPS6KB2 in the frontal cortex for WFT, and CSPG5 in the hypothalamus for DSST. These findings provide new information about the genetic determinants of cognitive function in this unique population. In addition, we derived a measure of general cognitive function based on these cognitive tests and generated genome-wide association summary results, providing a resource to the research community for comparison, replication, and meta-analysis in future genetic studies in Hispanics/Latinos.

}, keywords = {Aged, Cognition, Genome-Wide Association Study, Hispanic or Latino, Humans, Middle Aged, Neuropsychological tests, Public Health, Ubiquitin-Conjugating Enzymes}, issn = {2158-3188}, doi = {10.1038/s41398-020-00930-2}, author = {Jian, Xueqiu and Sofer, Tamar and Wassim Tarraf and Bressler, Jan and Jessica Faul and Zhao, Wei and Scott M Ratliff and Lamar, Melissa and Lenore J Launer and Laurie, Cathy C and Schneiderman, Neil and David R Weir and Wright, Clinton B and Kristine Yaffe and Zeng, Donglin and DeCarli, Charles and Thomas H Mosley and Smith, Jennifer A and Hector M Gonz{\'a}lez and Myriam Fornage} } @article {10355, title = {The Health and Retirement Study Harmonized Cognitive Assessment Protocol Project: Study Design and Methods}, journal = {Neuroepidemiology}, year = {2020}, month = {2019}, abstract = {Introduction: The Harmonized Cognitive Assessment Protocol (HCAP) Project is a substudy within the Health and Retirement Study (HRS), an ongoing nationally representative panel study of about 20,000 adults aged 51 or older in the United States. The HCAP is part of an international research collaboration funded by the National Institute on Aging to better measure and identify cognitive impairment and dementia in representative population-based samples of older adults, in the context of ongoing longitudinal studies of aging in high-, middle-, and low-income countries around the world. Methods: The HCAP cognitive test battery was designed to measure a range of key cognitive domains affected by cognitive aging (including attention, memory, executive function, language, and visuospatial function) and to allow harmonization and comparisons to other studies in the United States and around the world. The HCAP included a pair of in-person interviews, one with the target HRS respondent (a randomly selected HRS sample member, aged 65+) that lasted approximately 1 h and one with an informant nominated by the respondent that lasted approximately 20 min. The final HRS HCAP sample included 3,496 study subjects, representing a 79\% response rate among those invited to participate. Conclusion: Linking detailed HCAP cognitive assessments to the wealth of available longitudinal HRS data on cognition, health, biomarkers, genetics, health care utilization, informal care, and economic resources and behavior will provide unique and expanded opportunities to study cognitive impairment and dementia in a nationally representative US population-based sample. The fielding of similar HCAP projects in multiple countries around the world will provide additional opportunities to study international differences in the prevalence, incidence, and outcomes of dementia globally with comparable data. Like all HRS data, HCAP data are publicly available at no cost to researchers.}, keywords = {Cognition, cognitive assessment, study design}, isbn = {0251-5350}, doi = {10.1159/000503004}, author = {Kenneth M. Langa and Lindsay H Ryan and Ryan J McCammon and Richard N Jones and Jennifer J Manly and Deborah A Levine and Amanda Sonnega and Farron, M. and David R Weir} } @article {12124, title = {Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci.}, journal = {Molecular Psychiatry}, volume = {25}, year = {2020}, pages = {2392-2409}, abstract = {

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to~346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 {\texttimes} 10 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 {\texttimes} 10) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 {\texttimes} 10) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.

}, keywords = {Biological Specimen Banks, Databases, Factual, Europe, Exome, Female, Genetic Loci, Humans, Male, Polymorphism, Single Nucleotide, Smoking, United Kingdom}, issn = {1476-5578}, doi = {10.1038/s41380-018-0313-0}, author = {Erzurumluoglu, A Mesut and Liu, Mengzhen and Jackson, Victoria E and Barnes, Daniel R and Datta, Gargi and Melbourne, Carl A and Young, Robin and Batini, Chiara and Surendran, Praveen and Jiang, Tao and Adnan, Sheikh Daud and Afaq, Saima and Agrawal, Arpana and Altmaier, Elisabeth and Antoniou, Antonis C and Asselbergs, Folkert W and Baumbach, Clemens and Laura Bierut and Bertelsen, Sarah and Boehnke, Michael and Bots, Michiel L and Brazel, David M and Chambers, John C and Chang-Claude, Jenny and Chen, Chu and Corley, Janie and Chou, Yi-Ling and David, Sean P and de Boer, Rudolf A and Christiaan de Leeuw and Joe G Dennis and Dominiczak, Anna F and Dunning, Alison M and Easton, Douglas F and Charles B Eaton and Elliott, Paul and Evangelou, Evangelos and Jessica Faul and Tatiana Foroud and Goate, Alison and Gong, Jian and Hans-J{\"o}rgen Grabe and Jeffrey Haessler and Christopher A Haiman and Hallmans, G{\"o}ran and Anke R Hammerschlag and Sarah E Harris and Andrew T Hattersley and Andrew C Heath and Hsu, Chris and Iacono, William G and Kanoni, Stavroula and Kapoor, Manav and Kaprio, Jaakko and Sharon L R Kardia and Karpe, Fredrik and Kontto, Jukka and Kooner, Jaspal S and Charles Kooperberg and Kuulasmaa, Kari and Laakso, Markku and Lai, Dongbing and Langenberg, Claudia and Le, Nhung and Lettre, Guillaume and Loukola, Anu and Luan, Jian{\textquoteright}an and Pamela A F Madden and Mangino, Massimo and Riccardo E Marioni and Marouli, Eirini and Marten, Jonathan and Nicholas G Martin and McGue, Matt and Michailidou, Kyriaki and Mihailov, Evelin and Moayyeri, Alireza and Moitry, Marie and M{\"u}ller-Nurasyid, Martina and Naheed, Aliya and Nauck, Matthias and Neville, Matthew J and Sune Fallgaard Nielsen and Kari E North and Markus Perola and Pharoah, Paul D P and Pistis, Giorgio and Tinca J Polderman and Posthuma, Danielle and Neil Poulter and Qaiser, Beenish and Rasheed, Asif and Reiner, Alex and Renstrom, Frida and Rice, John and Rohde, Rebecca and Rolandsson, Olov and Nilesh J Samani and Samuel, Maria and Schlessinger, David and H Steven Scholte and Scott, Robert A and Peter Sever and Shao, Yaming and Shrine, Nick and Smith, Jennifer A and John M Starr and Kathleen E Stirrups and Stram, Danielle and Heather M Stringham and Tachmazidou, Ioanna and Tardif, Jean-Claude and Thompson, Deborah J and Hilary A Tindle and Tragante, Vinicius and Trompet, Stella and Turcot, Val{\'e}rie and Tyrrell, Jessica and Vaartjes, Ilonca and Van Der Leij, Andries R and van der Meer, Peter and Varga, Tibor V and Verweij, Niek and V{\"o}lzke, Henry and Wareham, Nicholas J and Warren, Helen R and David R Weir and Weiss, Stefan and Wetherill, Leah and Yaghootkar, Hanieh and Yavas, Ersin and Jiang, Yu and Chen, Fang and Zhan, Xiaowei and Zhang, Weihua and Zhao, Wei and Zhao, Wei and Zhou, Kaixin and Amouyel, Philippe and Blankenberg, Stefan and Caulfield, Mark J and Chowdhury, Rajiv and Francesco Cucca and Ian J Deary and Deloukas, Panos and Di Angelantonio, Emanuele and Marco M Ferrario and Ferri{\`e}res, Jean and Franks, Paul W and Timothy M Frayling and Frossard, Philippe and Hall, Ian P and Caroline Hayward and Jansson, Jan-H{\r a}kan and Jukema, J Wouter and Kee, Frank and M{\"a}nnist{\"o}, Satu and Andres Metspalu and Munroe, Patricia B and B{\o}rge G Nordestgaard and Palmer, Colin N A and Veikko Salomaa and Sattar, Naveed and Timothy Spector and David P Strachan and van der Harst, Pim and Zeggini, Eleftheria and Saleheen, Danish and Adam S Butterworth and Wain, Louise V and Gon{\c c}alo R Abecasis and Danesh, John and Tobin, Martin D and Scott Vrieze and Liu, Dajiang J and Howson, Joanna M M} } @article {12368, title = {Recent trends in wealth inequality among older Americans in two surveys}, journal = {Journal of Economics and Social Measurement}, volume = {45}, year = {2020}, pages = {215-236}, abstract = {We document changes in wealth inequality across American households with a member aged 55 or older, comparing data in the Health and Retirement Study (HRS) with that in the Survey of Consumer Finances (SCF) between 1998 and 2016. We examine net wealth including housing, financial and nonfinancial assets and debt, without the cash value of insurances, DB pensions or Social Security wealth. We find very similar distributions of net wealth in the two surveys between the 25th and 90th percentiles, but substantially higher wealth in the SCF at the top of the distribution. Both surveys show an increase in wealth inequality between 1998 and 2016, first mostly due to increased wealth at the top, and, after 2012, due to an increase in the share of households with very little wealth as well. Both surveys agree that wealth inequality by education and race, already substantial in 1998, increased further by 2016.}, keywords = {Education, net wealth, race disparity, social security wealth, Wealth Inequality}, doi = {10.3233/jem-210477}, author = {Kezdi, Gabor and Margaret Lay and David R Weir} } @article {12122, title = {Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.}, journal = {Nature Genetics}, volume = {51}, year = {2019}, pages = {237-244}, abstract = {

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders. They are heritable and etiologically related behaviors that have been resistant to gene discovery efforts. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures.

}, keywords = {Alcohol Drinking, Female, Genetic Variation, Genome-Wide Association Study, Humans, Male, Middle Aged, Phenotype, Risk, Smoking, Tobacco, Tobacco Use Disorder}, issn = {1546-1718}, doi = {10.1038/s41588-018-0307-5}, author = {Liu, Mengzhen and Jiang, Yu and Wedow, Robbee and Li, Yue and Brazel, David M and Chen, Fang and Datta, Gargi and Davila-Velderrain, Jose and McGuire, Daniel and Tian, Chao and Zhan, Xiaowei and Choquet, H{\'e}l{\`e}ne and Docherty, Anna R and Jessica Faul and Foerster, Johanna R and Fritsche, Lars G and Gabrielsen, Maiken Elvestad and Gordon, Scott D and Jeffrey Haessler and Jouke-Jan Hottenga and Huang, Hongyan and Jang, Seon-Kyeong and Philip R Jansen and Ling, Yueh and M{\"a}gi, Reedik and Matoba, Nana and McMahon, George and Mulas, Antonella and Orr{\`u}, Valeria and Palviainen, Teemu and Anita Pandit and Reginsson, Gunnar W and Skogholt, Anne Heidi and Smith, Jennifer A and Taylor, Amy E and Turman, Constance and Gonneke Willemsen and Young, Hannah and Young, Kendra A and Zajac, Gregory J M and Zhao, Wei and Zhou, Wei and Bjornsdottir, Gyda and Boardman, Jason D and Boehnke, Michael and Dorret I Boomsma and Chen, Chu and Francesco Cucca and Davies, Gareth E and Charles B Eaton and Ehringer, Marissa A and T{\~o}nu Esko and Fiorillo, Edoardo and Gillespie, Nathan A and Gudbjartsson, Daniel F and Haller, Toomas and Kathleen Mullan Harris and Andrew C Heath and Hewitt, John K and Hickie, Ian B and Hokanson, John E and Hopfer, Christian J and Hunter, David J and Iacono, William G and Johnson, Eric O and Kamatani, Yoichiro and Sharon L R Kardia and Matthew C Keller and Kellis, Manolis and Charles Kooperberg and Kraft, Peter and Krauter, Kenneth S and Laakso, Markku and Penelope A Lind and Loukola, Anu and Lutz, Sharon M and Pamela A F Madden and Nicholas G Martin and McGue, Matt and Matthew B McQueen and Sarah E Medland and Andres Metspalu and Mohlke, Karen L and Nielsen, Jonas B and Okada, Yukinori and Peters, Ulrike and Tinca J Polderman and Posthuma, Danielle and Reiner, Alexander P and Rice, John P and Rimm, Eric and Rose, Richard J and Runarsdottir, Valgerdur and Stallings, Michael C and Stan{\v c}{\'a}kov{\'a}, Alena and Stefansson, Hreinn and Thai, Khanh K and Hilary A Tindle and Tyrfingsson, Thorarinn and Wall, Tamara L and David R Weir and Weisner, Constance and Whitfield, John B and Winsvold, Bendik Slagsvold and Yin, Jie and Zuccolo, Luisa and Laura Bierut and Hveem, Kristian and Lee, James J and Munaf{\`o}, Marcus R and Saccone, Nancy L and Willer, Cristen J and Marilyn C Cornelis and David, Sean P and Hinds, David A and Jorgenson, Eric and Kaprio, Jaakko and Stitzel, Jerry A and Stefansson, Kari and Thorgeirsson, Thorgeir E and Gon{\c c}alo R Abecasis and Liu, Dajiang J and Scott Vrieze} } @article {12125, title = {Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol~Use.}, journal = {Biological Psychiatry}, volume = {85}, year = {2019}, pages = {946-955}, abstract = {

BACKGROUND: Smoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk.

METHODS: We analyzed \~{}250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci.

RESULTS: Meta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1\% to 2.2\% of phenotypic variance, reflecting 11\% to 18\% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95\% credible intervals.

CONCLUSIONS: Rare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior.

}, keywords = {Alcohol Drinking, Databases, Genetic, Exome, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Oligonucleotide Array Sequence Analysis, Phenotype, Polymorphism, Single Nucleotide, Smoking}, issn = {1873-2402}, doi = {10.1016/j.biopsych.2018.11.024}, author = {Brazel, David M and Jiang, Yu and Hughey, Jordan M and Turcot, Val{\'e}rie and Zhan, Xiaowei and Gong, Jian and Batini, Chiara and Weissenkampen, J Dylan and Liu, Mengzhen and Barnes, Daniel R and Bertelsen, Sarah and Chou, Yi-Ling and Erzurumluoglu, A Mesut and Jessica Faul and Jeffrey Haessler and Anke R Hammerschlag and Hsu, Chris and Kapoor, Manav and Lai, Dongbing and Le, Nhung and Christiaan de Leeuw and Loukola, Anu and Mangino, Massimo and Melbourne, Carl A and Pistis, Giorgio and Qaiser, Beenish and Rohde, Rebecca and Shao, Yaming and Heather M Stringham and Wetherill, Leah and Zhao, Wei and Agrawal, Arpana and Laura Bierut and Chen, Chu and Charles B Eaton and Goate, Alison and Christopher A Haiman and Andrew C Heath and Iacono, William G and Nicholas G Martin and Tinca J Polderman and Reiner, Alex and Rice, John and Schlessinger, David and H Steven Scholte and Smith, Jennifer A and Tardif, Jean-Claude and Hilary A Tindle and Van Der Leij, Andries R and Boehnke, Michael and Chang-Claude, Jenny and Francesco Cucca and David, Sean P and Tatiana Foroud and Howson, Joanna M M and Sharon L R Kardia and Charles Kooperberg and Laakso, Markku and Lettre, Guillaume and Pamela A F Madden and McGue, Matt and Kari E North and Posthuma, Danielle and Timothy Spector and Stram, Daniel and Tobin, Martin D and David R Weir and Kaprio, Jaakko and Gon{\c c}alo R Abecasis and Liu, Dajiang J and Scott Vrieze} } @article {10225, title = {A meta-analysis of genome-wide association studies identifies multiple longevity genes.}, journal = {Nature Communications}, volume = {10}, year = {2019}, month = {08/2019}, pages = {3669}, abstract = {

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.

}, keywords = {genes, Genome-Wide Association Study, GWA, longevity genes, meta-analysis}, issn = {2041-1723}, doi = {10.1038/s41467-019-11558-2}, url = {https://www.ncbi.nlm.nih.gov/pubmed/31413261}, author = {Deelen, Joris and Daniel S Evans and Dan E Arking and Tesi, Niccol{\`o} and Nygaard, Marianne and Liu, Xiaomin and Wojczynski, Mary K and Biggs, Mary L and van der Spek, Ashley and Atzmon, Gil and Erin B Ware and Sarnowski, Chlo{\'e} and Albert Vernon Smith and Sepp{\"a}l{\"a}, Ilkka and Cordell, Heather J and Dose, Janina and Amin, Najaf and Alice M. Arnold and Kristin L. Ayers and Barzilai, Nir and Becker, Elizabeth J and Beekman, Marian and Blanch{\'e}, H{\'e}l{\`e}ne and Christensen, Kaare and Christiansen, Lene and Collerton, Joanna C and Cubaynes, Sarah and Steven R Cummings and Davies, Karen and Debrabant, Birgit and Deleuze, Jean-Fran{\c c}ois and Duncan, Rachel and Jessica Faul and Franceschi, Claudio and Galan, Pilar and Gudnason, Vilmundur and Tamara B Harris and Huisman, Martijn and Hurme, Mikko A and Jagger, Carol and Jansen, Iris and Jylh{\"a}, Marja and K{\"a}h{\"o}nen, Mika and Karasik, David and Sharon L R Kardia and Kingston, Andrew and Kirkwood, Thomas B L and Lenore J Launer and Lehtim{\"a}ki, Terho and Lieb, Wolfgang and Lyytik{\"a}inen, Leo-Pekka and Martin-Ruiz, Carmen and Min, Junxia and Nebel, Almut and Anne B Newman and Nie, Chao and Nohr, Ellen A and Orwoll, Eric S and Thomas T Perls and Province, Michael A and Psaty, Bruce M and Olli T Raitakari and Reinders, Marcel J T and Robine, Jean-Marie and Rotter, Jerome I and Sebastiani, Paola and Jennifer A Smith and S{\o}rensen, Thorkild I A and Kent D Taylor and Andr{\'e} G Uitterlinden and van der Flier, Wiesje and Sven J van der Lee and Cornelia M van Duijn and van Heemst, Diana and James W Vaupel and David R Weir and Ye, Kenny and Zeng, Yi and Zheng, Wanlin and Holstege, Henne and Douglas P Kiel and Kathryn L Lunetta and Eline P Slagboom and Joanne M Murabito} } @article {12128, title = {Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.}, journal = {Nature Communications}, volume = {10}, year = {2019}, pages = {376}, abstract = {

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Asians, Blacks, Brazil, Calcium-Binding Proteins, Cholesterol, Cholesterol, HDL, Cholesterol, LDL, Exercise, Female, Genetic Loci, Genome-Wide Association Study, Genotype, Hispanic or Latino, Humans, LIM-Homeodomain Proteins, Lipid Metabolism, Lipids, Male, Membrane Proteins, Microtubule-Associated Proteins, Middle Aged, Muscle Proteins, Nerve Tissue Proteins, Transcription Factors, Triglycerides, Whites, Young Adult}, issn = {2041-1723}, doi = {10.1038/s41467-018-08008-w}, author = {Kilpel{\"a}inen, Tuomas O and Bentley, Amy R and Noordam, Raymond and Yun Ju Sung and Schwander, Karen and Thomas W Winkler and Jakupovi{\'c}, Hermina and Daniel I Chasman and Alisa Manning and Ntalla, Ioanna and Aschard, Hugues and Brown, Michael R and de Las Fuentes, Lisa and Franceschini, Nora and Guo, Xiuqing and Vojinovic, Dina and Aslibekyan, Stella and Feitosa, Mary F and Kho, Minjung and Musani, Solomon K and Melissa Richard and Wang, Heming and Wang, Zhe and Traci M Bartz and Bielak, Lawrence F and Campbell, Archie and Dorajoo, Rajkumar and Fisher, Virginia and Hartwig, Fernando P and Horimoto, Andrea R V R and Li, Changwei and Kurt Lohman and Marten, Jonathan and Sim, Xueling and Smith, Albert V and Tajuddin, Salman M and Alver, Maris and Amini, Marzyeh and Boissel, Mathilde and Jin-Fang Chai and Chen, Xu and Divers, Jasmin and Evangelou, Evangelos and Gao, Chuan and Graff, Mariaelisa and Sarah E Harris and He, Meian and Hsu, Fang-Chi and Jackson, Anne U and Jing Hua Zhao and Kraja, Aldi T and K{\"u}hnel, Brigitte and Laguzzi, Federica and Lyytik{\"a}inen, Leo-Pekka and Ilja M Nolte and Rauramaa, Rainer and Riaz, Muhammad and Robino, Antonietta and Rueedi, Rico and Heather M Stringham and Takeuchi, Fumihiko and van der Most, Peter J and Varga, Tibor V and Verweij, Niek and Erin B Ware and Wen, Wanqing and Li, Xiaoyin and Yanek, Lisa R and Amin, Najaf and Donna K Arnett and Boerwinkle, Eric and Brumat, Marco and Brian E Cade and Canouil, Micka{\"e}l and Chen, Yii-Der Ida and Concas, Maria Pina and Connell, John and de Mutsert, Ren{\'e}e and de Silva, H Janaka and de Vries, Paul S and Demirkan, Ayse and Ding, Jingzhong and Charles B Eaton and Jessica Faul and Friedlander, Yechiel and Gabriel, Kelley P and Ghanbari, Mohsen and Giulianini, Franco and Gu, Chi Charles and Gu, Dongfeng and Tamara B Harris and He, Jiang and Heikkinen, Sami and Heng, Chew-Kiat and Hunt, Steven C and Ikram, M Arfan and Jost Bruno Jonas and Koh, Woon-Puay and Komulainen, Pirjo and Krieger, Jose E and Stephen B Kritchevsky and Kutalik, Zolt{\'a}n and Kuusisto, Johanna and Langefeld, Carl D and Langenberg, Claudia and Lenore J Launer and Leander, Karin and Lemaitre, Rozenn N and Lewis, Cora E and Liang, Jingjing and Liu, Jianjun and M{\"a}gi, Reedik and Manichaikul, Ani and Meitinger, Thomas and Andres Metspalu and Milaneschi, Yuri and Mohlke, Karen L and Thomas H Mosley and Murray, Alison D and Michael A Nalls and Nang, Ei-Ei Khaing and Nelson, Christopher P and Nona, Sotoodehnia and Norris, Jill M and Nwuba, Chiamaka Vivian and Jeff O{\textquoteright}Connell and Palmer, Nicholette D and Papanicolau, George J and Pazoki, Raha and Nancy L Pedersen and Peters, Annette and Peyser, Patricia A and Polasek, Ozren and David J Porteous and Poveda, Alaitz and Olli T Raitakari and Rich, Stephen S and Neil Risch and Robinson, Jennifer G and Rose, Lynda M and Rudan, Igor and Schreiner, Pamela J and Scott, Robert A and Stephen Sidney and Sims, Mario and Smith, Jennifer A and Snieder, Harold and Sofer, Tamar and John M Starr and Sternfeld, Barbara and Strauch, Konstantin and Tang, Hua and Kent D Taylor and Tsai, Michael Y and Tuomilehto, Jaakko and Andr{\'e} G Uitterlinden and van der Ende, M Yldau and van Heemst, Diana and Voortman, Trudy and Waldenberger, Melanie and Wennberg, Patrik and Wilson, Gregory and Xiang, Yong-Bing and Yao, Jie and Yu, Caizheng and Yuan, Jian-Min and Zhao, Wei and Alan B Zonderman and Becker, Diane M and Boehnke, Michael and Bowden, Donald W and de Faire, Ulf and Ian J Deary and Elliott, Paul and T{\~o}nu Esko and Freedman, Barry I and Froguel, Philippe and Paolo P. Gasparini and Gieger, Christian and Kato, Norihiro and Laakso, Markku and Lakka, Timo A and Lehtim{\"a}ki, Terho and Patrik K E Magnusson and Oldehinkel, Albertine J and Brenda W J H Penninx and Nilesh J Samani and Shu, Xiao-Ou and van der Harst, Pim and Jana V. van Vliet-Ostaptchouk and Vollenweider, Peter and Wagenknecht, Lynne E and Wang, Ya X and Wareham, Nicholas J and David R Weir and Wu, Tangchun and Zheng, Wei and Zhu, Xiaofeng and Michele K Evans and Franks, Paul W and Gudnason, Vilmundur and Caroline Hayward and Horta, Bernardo L and Tanika N Kelly and Liu, Yongmei and Kari E North and Pereira, Alexandre C and Ridker, Paul M and Tai, E Shyong and van Dam, Rob M and Fox, Ervin R and Sharon L R Kardia and Liu, Ching-Ti and Dennis O Mook-Kanamori and Province, Michael A and Redline, Susan and Cornelia M van Duijn and Rotter, Jerome I and Charles Kooperberg and Gauderman, W James and Psaty, Bruce M and Kenneth Rice and Munroe, Patricia B and Myriam Fornage and Cupples, L Adrienne and Charles N Rotimi and Alanna C Morrison and Rao, Dabeeru C and Ruth J F Loos} } @article {12123, title = {New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders.}, journal = {Nature Human Behaviour}, volume = {3}, year = {2019}, pages = {950-961}, abstract = {

Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g d) from the UK Biobank, the Alcohol Genome-Wide Consortium and the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus consortia, collecting data from 480,842 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 new common loci and investigated their potential functional importance using magnetic resonance imaging data and gene expression studies. We identify genetic pathways associated with alcohol consumption and suggest genetic mechanisms that are shared with neuropsychiatric disorders such as schizophrenia.

}, keywords = {Adult, Aged, Alcohol Drinking, Alcoholism, Brain, Female, genes, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Magnetic Resonance Imaging, Male, Mental Disorders, Middle Aged, Neuroimaging, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Schizophrenia, Whites}, issn = {2397-3374}, doi = {10.1038/s41562-019-0653-z}, author = {Evangelou, Evangelos and Gao, He and Chu, Congying and Ntritsos, Georgios and Blakeley, Paul and Butts, Andrew R and Pazoki, Raha and Suzuki, Hideaki and Koskeridis, Fotios and Yiorkas, Andrianos M and Karaman, Ibrahim and Elliott, Joshua and Luo, Qiang and Aeschbacher, Stefanie and Traci M Bartz and Baumeister, Sebastian E and Braund, Peter S and Brown, Michael R and Brody, Jennifer A and Clarke, Toni-Kim and Dimou, Niki and Jessica Faul and Homuth, Georg and Jackson, Anne U and Kentistou, Katherine A and Joshi, Peter K and Lemaitre, Rozenn N and Penelope A Lind and Lyytik{\"a}inen, Leo-Pekka and Mangino, Massimo and Milaneschi, Yuri and Nelson, Christopher P and Ilja M Nolte and Per{\"a}l{\"a}, Mia-Maria and Polasek, Ozren and David J Porteous and Scott M Ratliff and Smith, Jennifer A and Stan{\v c}{\'a}kov{\'a}, Alena and Teumer, Alexander and Tuominen, Samuli and Th{\'e}riault, S{\'e}bastien and Vangipurapu, Jagadish and Whitfield, John B and Wood, Alexis and Yao, Jie and Yu, Bing and Zhao, Wei and Dan E Arking and Auvinen, Juha and Liu, Chunyu and M{\"a}nnikk{\"o}, Minna and Risch, Lorenz and Rotter, Jerome I and Snieder, Harold and Veijola, Juha and Alexandra I Blakemore and Boehnke, Michael and Campbell, Harry and Conen, David and Johan G Eriksson and Hans-J{\"o}rgen Grabe and Guo, Xiuqing and van der Harst, Pim and Catharina A Hartman and Caroline Hayward and Andrew C Heath and J{\"a}rvelin, Marjo-Riitta and K{\"a}h{\"o}nen, Mika and Sharon L R Kardia and K{\"u}hne, Michael and Kuusisto, Johanna and Laakso, Markku and Lahti, Jari and Lehtim{\"a}ki, Terho and McIntosh, Andrew M and Mohlke, Karen L and Alanna C Morrison and Nicholas G Martin and Oldehinkel, Albertine J and Brenda W J H Penninx and Psaty, Bruce M and Olli T Raitakari and Rudan, Igor and Nilesh J Samani and Scott, Laura J and Timothy Spector and Verweij, Niek and David R Weir and James F Wilson and Levy, Daniel and Tzoulaki, Ioanna and Bell, Jimmy D and Matthews, Paul M and Rothenfluh, Adrian and Desrivi{\`e}res, Sylvane and Schumann, Gunter and Elliott, Paul} } @article {9010, title = {Widowhood and Depression in a Cross-National Perspective: Evidence from the United States, Europe, Korea, and China.}, journal = {The Journals of Gerontology: Series B}, volume = {73}, year = {2019}, pages = {e143-e153}, abstract = {

Objectives: We explore marital and depression trajectories over time for men and women, and distinguish between mood and somatic depression across contexts.

Method: We use longitudinal data from 2002 to 2013 from the United States, England, Europe, Korea, and China to explore depression among individuals married at baseline and follow their trajectories into widowhood with married as the reference group. We use random effects models to estimate these trajectories using the Center for Epidemiologic Studies Depression Scale (CES-D) or EURO-D scales for men and women.

Results: Depression peaks within the first year of widowhood for men and women, but women recover to levels comparable to married counterparts in all countries. Men sustain high levels of depression even 6-10 years post-widowhood everywhere except Europe. Widowed women have higher somatic depression compared to men, who have higher mood depression. Family plays differential roles in mediating depression across countries.

Discussion: Our research shows the complex global relationship between widowhood and depression. Studies that do not compare depression trajectories over time may make incorrect inferences about the persistence of depression by gender and country. Interventions should target different components of depression: mood-related symptoms for men and somatic-related symptoms for women for most effective recovery.

}, keywords = {Bereavement, CHARLS, Cross-National, Depressive symptoms, ELSA, KLoSA, SHARE}, issn = {1758-5368}, doi = {10.1093/geronb/gbx021}, author = {Jadhav, Apoorva and David R Weir} } @inbook {10190, title = {Biomarkers in Representative Population Surveys.}, booktitle = {The Palgrave Handbook of Survey Research}, year = {2018}, pages = {227-233}, publisher = {Palgrave Macmillan, Cham}, organization = {Palgrave Macmillan, Cham}, abstract = {Objective measures of health indicators have historically been very challenging to collect with large-scale representative population surveys. Cost, interviewer training, and the invasiveness of collection techniques were some of the primary barriers. However new methods in biological specimen or biomarker collection and analysis mean that a number of these barriers have been reduced or removed. This chapter discusses some of the existing studies that collect biomarkers in the United States as example cases for how new developments have changed the viability of collecting these measures at scale. In particular, dried blood spot (DBS) and DNA sampling and analysis are discussed as groundbreaking advancements in this area of data collection.}, keywords = {Biomarkers}, isbn = {978-3-319-54395-6}, doi = {https://doi.org/10.1007/978-3-319-54395-6}, url = {https://link.springer.com/chapter/10.1007\%2F978-3-319-54395-6_29}, author = {David R Weir} } @article {11949, title = {Effect of delayed cell processing and cryopreservation on immunophenotyping in multicenter population studies.}, journal = {Journal of Immunological Methods}, volume = {463}, year = {2018}, pages = {61-70}, abstract = {

Variability induced by delayed cell processing and cell cryopreservation presents unique challenges for immunophenotyping in large population studies. We conducted a pilot study to evaluate the effect of delayed cell processing and cryopreservation on cell percentages obtained by immunophenotyping. We collected blood from 20 volunteers and compared the effect of (a) delayed cell processing up to 72 h (b) cryopreservation and (c) the combined effect of delayed cell processing and cryopreservation on immunophenotyping of 31 cell subsets that included several subsets of T, B, Natural Killer (NK) cells, monocytes and dendritic cells using both whole blood collected in EDTA tubes and peripheral blood mononuclear cells collected in CPT tubes. We found the delayed cell processing up to 72 h or cryopreservation alone did not significantly affect the percentages T cells, dendritic cells or monocytes but significantly increased the percentage of B cells and NK cells (p for trend <=0.01) but. However combination of delayed cell processing up to 72 h and cryopreservation significantly increased the percentage of T cells as compared to cells processed immediately (p for trend <0.0001) while a delayed cell processing followed by cryopreservation decreased the percentage of NK cells (p for trend <0.0001). Total B-cells increased significantly with a 24-48 h delay in cell processing and cryopreservation but not at 72 h. The percentages of monocytes and dendritic cells remained unaffected by the combination of delayed cell processing and cryopreservation. These findings suggest that immunophenotyping of several immune cell subsets can be successfully implemented in large population studies as long as blood is processed within 48 h of biospecimen collection though some cell subsets may be more susceptible to a combination of delayed cell processing and cryopreservation.

}, keywords = {Cell Separation, Cryopreservation, Immunophenotyping, Leukocytes, Time Factors}, issn = {1872-7905}, doi = {10.1016/j.jim.2018.09.007}, author = {Bharat Thyagarajan and Barcelo, Helene and Eileen M. Crimmins and David R Weir and Minnerath, Sharon and Vivek, Sithara and Jessica Faul} } @inbook {10191, title = {New Measures and New Designs in Demography of Aging Research}, booktitle = {Future Directions for the Demography of Aging: Proceedings of a Workshop }, year = {2018}, pages = {371-396}, publisher = {The National Academies Press}, organization = {The National Academies Press}, chapter = {13}, address = {Washington, DC}, abstract = {A volume devoted to the demography of aging does well to recognize the importance of innovative data collection and data sharing. The field has been a leader in developing new designs and measurement approaches, and these studies in turn have shaped and pushed the research frontier for the study of aging. The strong commitment to data sharing with open access to the data for the scientific community{\textemdash}and the resulting high volume of research{\textemdash}has begun to influence other related fields. The National Institute on Aging (NIA), and in particular its branch of Behavioral and Social Research, has been the primary force behind this empirical infrastructure, providing funding, scientific leadership, and encouraging collaboration across the studies it supports and beyond.}, isbn = {978-0-309-47413-9}, doi = {https://doi.org/10.17226/25064}, url = {https://www.nap.edu/read/25064/chapter/21}, author = {David R Weir and Linda J. Waite and Wong, R. and Vicki A Freedman} } @article {12139, title = {Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.}, journal = {Nature Communications}, volume = {9}, year = {2018}, pages = {2098}, abstract = {

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 {\texttimes} 10) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3\% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Cognition, Genetic Loci, Genetic Predisposition to Disease, Humans, Mental Disorders, Middle Aged, Multifactorial Inheritance, Neurodegenerative Diseases, Neurodevelopmental Disorders, Polymorphism, Single Nucleotide, Reaction Time, Young Adult}, issn = {2041-1723}, doi = {10.1038/s41467-018-04362-x}, author = {Gail Davies and Lam, Max and Sarah E Harris and Joey W Trampush and Luciano, Michelle and W David Hill and Hagenaars, Saskia P and Ritchie, Stuart J and Riccardo E Marioni and Fawns-Ritchie, Chloe and David C Liewald and Okely, Judith A and Ahola-Olli, Ari V and Barnes, Catriona L K and Bertram, Lars and Joshua C. Bis and Katherine E Burdick and Christoforou, Andrea and DeRosse, Pamela and Djurovic, Srdjan and Espeseth, Thomas and Giakoumaki, Stella and Giddaluru, Sudheer and Gustavson, Daniel E and Caroline Hayward and Edith Hofer and Ikram, M Arfan and Karlsson, Robert and Knowles, Emma and Lahti, Jari and Leber, Markus and Li, Shuo and Mather, Karen A and Melle, Ingrid and Morris, Derek and Christopher J Oldmeadow and Palviainen, Teemu and Payton, Antony and Pazoki, Raha and Katja E Petrovic and Chandra A Reynolds and Sargurupremraj, Muralidharan and Scholz, Markus and Smith, Jennifer A and Smith, Albert V and Terzikhan, Natalie and Thalamuthu, Anbupalam and Trompet, Stella and Sven J van der Lee and Erin B Ware and Windham, B Gwen and Margaret J Wright and Yang, Jingyun and Yu, Jin and Ames, David and Amin, Najaf and Amouyel, Philippe and Andreassen, Ole A and Armstrong, Nicola J and Assareh, Amelia A and John R. Attia and Attix, Deborah and Avramopoulos, Dimitrios and David A Bennett and B{\"o}hmer, Anne C and Patricia A. Boyle and Brodaty, Henry and Campbell, Harry and Tyrone D. Cannon and Elizabeth T. Cirulli and Congdon, Eliza and Conley, Emily Drabant and Corley, Janie and Cox, Simon R and Dale, Anders M and Dehghan, Abbas and Danielle M. Dick and Dickinson, Dwight and Johan G Eriksson and Evangelou, Evangelos and Jessica Faul and Ford, Ian and Nelson A. Freimer and Gao, He and Giegling, Ina and Gillespie, Nathan A and Gordon, Scott D and Gottesman, Rebecca F and Michael E Griswold and Gudnason, Vilmundur and Tamara B Harris and Hartmann, Annette M and Hatzimanolis, Alex and Gerardo Heiss and Holliday, Elizabeth G and Joshi, Peter K and K{\"a}h{\"o}nen, Mika and Sharon L R Kardia and Ida Karlsson and Kleineidam, Luca and David S Knopman and Kochan, Nicole A and Konte, Bettina and Kwok, John B and Stephanie Le Hellard and Lee, Teresa and Lehtim{\"a}ki, Terho and Li, Shu-Chen and Lill, Christina M and Liu, Tian and Koini, Marisa and London, Edythe and Longstreth, Will T and Lopez, Oscar L and Loukola, Anu and Luck, Tobias and Astri J Lundervold and Lundquist, Anders and Lyytik{\"a}inen, Leo-Pekka and Nicholas G Martin and Grant W Montgomery and Murray, Alison D and Anna C Need and Noordam, Raymond and Nyberg, Lars and William E R Ollier and Papenberg, Goran and Pattie, Alison and Polasek, Ozren and Russell A Poldrack and Psaty, Bruce M and Reppermund, Simone and Steffi G Riedel-Heller and Rose, Richard J and Rotter, Jerome I and Roussos, Panos and Rovio, Suvi P and Saba, Yasaman and Fred W Sabb and Sachdev, Perminder S and Satizabal, Claudia L and Schmid, Matthias and Rodney J Scott and Matthew A Scult and Simino, Jeannette and Slagboom, P Eline and Smyrnis, Nikolaos and Soumar{\'e}, A{\"\i}cha and Nikos C Stefanis and Stott, David J and Richard E Straub and Sundet, Kjetil and Taylor, Adele M and Kent D Taylor and Tzoulaki, Ioanna and Tzourio, Christophe and Andr{\'e} G Uitterlinden and Vitart, Veronique and Aristotle N Voineskos and Kaprio, Jaakko and Wagner, Michael and Wagner, Holger and Weinhold, Leonie and Wen, K Hoyan and Elisabeth Widen and Yang, Qiong and Zhao, Wei and Hieab H Adams and Dan E Arking and Robert M Bilder and Bitsios, Panos and Boerwinkle, Eric and Chiba-Falek, Ornit and Corvin, Aiden and Philip L de Jager and Debette, St{\'e}phanie and Donohoe, Gary and Elliott, Paul and Fitzpatrick, Annette L and Gill, Michael and David C. Glahn and H{\"a}gg, Sara and Narelle K Hansell and Ahmad R Hariri and Ikram, M Kamran and Jukema, J Wouter and Vuoksimaa, Eero and Matthew C Keller and Kremen, William S and Lenore J Launer and Lindenberger, Ulman and Aarno Palotie and Nancy L Pedersen and Pendleton, Neil and David J Porteous and Katri R{\"a}ikk{\"o}nen and Olli T Raitakari and Ramirez, Alfredo and Reinvang, Ivar and Rudan, Igor and Schmidt, Reinhold and Schmidt, Helena and Peter W Schofield and Peter R Schofield and John M Starr and Vidar M Steen and Trollor, Julian N and Turner, Steven T and Cornelia M van Duijn and Villringer, Arno and Daniel R Weinberger and David R Weir and James F Wilson and Anil K. Malhotra and McIntosh, Andrew M and Gale, Catharine R and Seshadri, Sudha and Thomas H Mosley and Bressler, Jan and Lencz, Todd and Ian J Deary} } @article {12135, title = {An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype.}, journal = {Biological Psychiatry}, volume = {82}, year = {2017}, pages = {322-329}, abstract = {

BACKGROUND: The genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder.

METHODS: We analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures.

RESULTS: The SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 {\texttimes} 10) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 {\texttimes} 10).

CONCLUSIONS: This large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression.

}, keywords = {Acid Anhydride Hydrolases, depression, Depressive Disorder, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Neoplasm Proteins, Phenotype, Whites}, issn = {1873-2402}, doi = {10.1016/j.biopsych.2016.11.013}, author = {Nese Direk and Williams, Stephanie and Smith, Jennifer A and Ripke, Stephan and Air, Tracy and Amare, Azmeraw T and Amin, Najaf and Baune, Bernhard T and David A Bennett and Blackwood, Douglas H R and Dorret I Boomsma and Breen, Gerome and Buttensch{\o}n, Henriette N and Byrne, Enda M and B{\o}rglum, Anders D and Castelao, Enrique and Cichon, Sven and Clarke, Toni-Kim and Marilyn C Cornelis and Dannlowski, Udo and Philip L de Jager and Demirkan, Ayse and Domenici, Enrico and Cornelia M van Duijn and Dunn, Erin C and Johan G Eriksson and T{\~o}nu Esko and Jessica Faul and Luigi Ferrucci and Myriam Fornage and Eco J. C. de Geus and Gill, Michael and Gordon, Scott D and Hans-J{\"o}rgen Grabe and van Grootheest, Gerard and Hamilton, Steven P and Catharina A Hartman and Andrew C Heath and Karin Hek and Hofman, Albert and Homuth, Georg and Horn, Carsten and Jouke-Jan Hottenga and Sharon L R Kardia and Kloiber, Stefan and Karestan C Koenen and Kutalik, Zolt{\'a}n and Ladwig, Karl-Heinz and Lahti, Jari and Douglas F Levinson and Lewis, Cathryn M and Lewis, Glyn and Li, Qingqin S and David J Llewellyn and Lucae, Susanne and Kathryn L Lunetta and MacIntyre, Donald J and Pamela A F Madden and Nicholas G Martin and McIntosh, Andrew M and Andres Metspalu and Milaneschi, Yuri and Grant W Montgomery and Mors, Ole and Thomas H Mosley and Joanne M Murabito and M{\"u}ller-Myhsok, Bertram and Markus M N{\"o}then and Nyholt, Dale R and O{\textquoteright}Donovan, Michael C and Brenda W J H Penninx and Pergadia, Michele L and Perlis, Roy and Potash, James B and Preisig, Martin and Shaun M Purcell and Quiroz, Jorge A and Katri R{\"a}ikk{\"o}nen and Rice, John P and Rietschel, Marcella and Rivera, Margarita and Schulze, Thomas G and Shi, Jianxin and Shyn, Stanley and Sinnamon, Grant C and Johannes H Smit and Smoller, Jordan W and Snieder, Harold and Toshiko Tanaka and Tansey, Katherine E and Teumer, Alexander and Uher, Rudolf and Umbricht, Daniel and Van der Auwera, Sandra and Erin B Ware and David R Weir and Weissman, Myrna M and Gonneke Willemsen and Yang, Jingyun and Zhao, Wei and Henning Tiemeier and Patrick F. Sullivan} } @article {8813, title = {A Comparison of the Prevalence of Dementia in the United States in 2000 and 2012.}, journal = {JAMA Intern Med}, volume = {177}, year = {2017}, month = {2017 01 01}, pages = {51-58}, abstract = {

Importance: The aging of the US population is expected to lead to a large increase in the number of adults with dementia, but some recent studies in the United States and other high-income countries suggest that the age-specific risk of dementia may have declined over the past 25 years. Clarifying current and future population trends in dementia prevalence and risk has important implications for patients, families, and government programs.

Objective: To compare the prevalence of dementia in the United States in 2000 and 2012.

Design, Setting, and Participants: We used data from the Health and Retirement Study (HRS), a nationally representative, population-based longitudinal survey of individuals in the United States 65 years or older from the 2000 (n = 10 546) and 2012 (n = 10 511) waves of the HRS.

Main Outcomes and Measures: Dementia was identified in each year using HRS cognitive measures and validated methods for classifying self-respondents, as well as those represented by a proxy. Logistic regression was used to identify socioeconomic and health variables associated with change in dementia prevalence between 2000 and 2012.

Results: The study cohorts had an average age of 75.0 years (95\% CI, 74.8-75.2 years) in 2000 and 74.8 years (95\% CI, 74.5-75.1 years) in 2012 (P = .24); 58.4\% (95\% CI, 57.3\%-59.4\%) of the 2000 cohort was female compared with 56.3\% (95\% CI, 55.5\%-57.0\%) of the 2012 cohort (P < .001). Dementia prevalence among those 65 years or older decreased from 11.6\% (95\% CI, 10.7\%-12.7\%) in 2000 to 8.8\% (95\% CI, 8.2\%-9.4\%) (8.6\% with age- and sex-standardization) in 2012 (P < .001). More years of education was associated with a lower risk for dementia, and average years of education increased significantly (from 11.8 years [95\% CI, 11.6-11.9 years] to 12.7 years [95\% CI, 12.6-12.9 years]; P < .001) between 2000 and 2012. The decline in dementia prevalence occurred even though there was a significant age- and sex-adjusted increase between years in the cardiovascular risk profile (eg, prevalence of hypertension, diabetes, and obesity) among older US adults.

Conclusions and Relevance: The prevalence of dementia in the United States declined significantly between 2000 and 2012. An increase in educational attainment was associated with some of the decline in dementia prevalence, but the full set of social, behavioral, and medical factors contributing to the decline is still uncertain. Continued monitoring of trends in dementia incidence and prevalence will be important for better gauging the full future societal impact of dementia as the number of older adults increases in the decades ahead.

}, keywords = {Aged, Dementia, Female, Humans, Male, Prevalence, Risk Factors, United States}, issn = {2168-6114}, doi = {10.1001/jamainternmed.2016.6807}, url = {http://archinte.jamanetwork.com/article.aspx?doi=10.1001/jamainternmed.2016.6807http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2587084}, author = {Kenneth M. Langa and Eric B Larson and Eileen M. Crimmins and Jessica Faul and Deborah A Levine and Mohammed U Kabeto and David R Weir} } @article {9172, title = {The complex genetics of gait speed: genome-wide meta-analysis approach.}, journal = {Aging (Albany NY)}, volume = {9}, year = {2017}, pages = {209-246}, abstract = {Emerging evidence suggests that the basis for variation in late-life mobility is attributable, in part, to genetic factors, which may become increasingly important with age. Our objective was to systematically assess the contribution of genetic variation to gait speed in older individuals. We conducted a meta-analysis of gait speed GWASs in 31,478 older adults from 17 cohorts of the CHARGE consortium, and validated our results in 2,588 older adults from 4 independent studies. We followed our initial discoveries with network and eQTL analysis of candidate signals in tissues. The meta-analysis resulted in a list of 536 suggestive genome wide significant SNPs in or near 69 genes. Further interrogation with Pathway Analysis placed gait speed as a polygenic complex trait in five major networks. Subsequent eQTL analysis revealed several SNPs significantly associated with the expression of PRSS16, WDSUB1 and PTPRT, which in addition to the meta-analysis and pathway suggested that genetic effects on gait speed may occur through synaptic function and neuronal development pathways. No genome-wide significant signals for gait speed were identified from this moderately large sample of older adults, suggesting that more refined physical function phenotypes will be needed to identify the genetic basis of gait speed in aging.}, keywords = {Genetics, GWAS}, issn = {1945-4589}, doi = {10.18632/aging.101151}, author = {Ben-Avraham, Dan and Karasik, David and Joe Verghese and Kathryn L Lunetta and John D Eicher and Vered, Rotem and Deelen, Joris and Alice M. Arnold and Aron S Buchman and Toshiko Tanaka and Jessica Faul and Nethander, Maria and Myriam Fornage and Hieab H Adams and Amy M Matteini and Michele L Callisaya and Albert Vernon Smith and Lei Yu and Philip L de Jager and Denis A Evans and Gudnason, Vilmundur and Hofman, Albert and Pattie, Alison and Corley, Janie and Lenore J Launer and David S Knopman and Parimi, Neeta and Stephen T Turner and Bandinelli, Stefania and Beekman, Marian and Gutman, Danielle and Sharvit, Lital and Simon P Mooijaart and David C Liewald and Jeanine J Houwing-Duistermaat and Ohlsson, Claes and Moed, Matthijs and Vincent J Verlinden and Mellstr{\"o}m, Dan and Jos N van der Geest and Karlsson, Magnus and Dena G Hernandez and McWhirter, Rebekah and Yongmei Liu and Thomson, Russell and Tranah, Gregory J and Andr{\'e} G Uitterlinden and David R Weir and Wei Zhao and John M Starr and Mohammed Arfan Ikram and David A Bennett and Steven R Cummings and Ian J Deary and Tamara B Harris and Sharon L R Kardia and Thomas H Mosley and Velandai K Srikanth and Beverly G Windham and Anne B Newman and Jeremy D Walston and Gail Davies and Daniel S Evans and Eline P Slagboom and Luigi Ferrucci and Douglas P Kiel and Joanne M Murabito and Atzmon, Gil} } @article {9326, title = {Contemporaneous Social Environment and the Architecture of Late-Life Gene Expression Profiles.}, journal = {American Journal of Epidemiology}, volume = {186}, year = {2017}, pages = {503-509}, abstract = {Environmental or social challenges can stimulate a cascade of coordinated physiological changes in stress response systems. Unfortunately, chronic activation of these adaptations under conditions such as low socioeconomic status (SES) can have negative consequences for long-term health. While there is substantial evidence tying low SES to increased disease risk and reduced life expectancy, the underlying biology remains poorly understood. Using pilot data on 120 older adults from the Health and Retirement Study (United States, 2002-2010), we examined the associations between SES and gene expression levels in adulthood, with particular focus on a gene expression program known as the conserved transcriptional response to adversity. We also used a bioinformatics-based approach to assess the activity of specific gene regulation pathways involved in inflammation, antiviral responses, and stress-related neuroendocrine signaling. We found that low SES was related to increased expression of conserved transcriptional response to adversity genes and distinct patterns of proinflammatory, antiviral, and stress signaling (e.g., sympathetic nervous system and hypothalamic-pituitary-adrenal axis) transcription factor activation.}, keywords = {Genetics, Socioeconomic factors}, issn = {1476-6256}, doi = {10.1093/aje/kwx147}, author = {Morgan E. Levine and Eileen M. Crimmins and David R Weir and Steven W. Cole} } @article {12136, title = {Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium.}, journal = {PLoS Genetics}, volume = {13}, year = {2017}, pages = {e1006719}, abstract = {

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5{\texttimes}10-8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (<5\%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P < 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained <= 20 variants in the credible sets that jointly account for 99\% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in identifying GWAS loci including low frequency variants. Trans-ethnic meta-analyses further improved fine mapping of putative causal variants in loci shared between the African and European ancestry populations.

}, keywords = {Adiposity, Anthropometry, Blacks, Body Mass Index, Chromosome Mapping, Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Obesity, Polymorphism, Single Nucleotide, Serine Endopeptidases, Transcription Factor 7-Like 2 Protein, Waist-Hip Ratio, Whites}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1006719}, author = {Ng, Maggie C Y and Graff, Mariaelisa and Lu, Yingchang and Justice, Anne E and Mudgal, Poorva and Liu, Ching-Ti and Young, Kristin and Yanek, Lisa R and Feitosa, Mary F and Wojczynski, Mary K and Rand, Kristin and Brody, Jennifer A and Brian E Cade and Dimitrov, Latchezar and Duan, Qing and Guo, Xiuqing and Leslie A Lange and Michael A Nalls and Okut, Hayrettin and Tajuddin, Salman M and Bamidele O Tayo and Vedantam, Sailaja and Bradfield, Jonathan P and Chen, Guanjie and Chen, Wei-Min and Chesi, Alessandra and Irvin, Marguerite R and Padhukasahasram, Badri and Smith, Jennifer A and Zheng, Wei and Matthew A. Allison and Ambrosone, Christine B and Bandera, Elisa V and Traci M Bartz and Berndt, Sonja I and Bernstein, Leslie and Blot, William J and Erwin P Bottinger and John Carpten and Chanock, Stephen J and Chen, Yii-Der Ida and Conti, David V and Cooper, Richard S and Myriam Fornage and Freedman, Barry I and Garcia, Melissa and Phyllis J Goodman and Hsu, Yu-Han H and Hu, Jennifer and Huff, Chad D and Ingles, Sue A and John, Esther M and Rick A Kittles and Eric A Klein and Li, Jin and McKnight, Barbara and Nayak, Uma and Nemesure, Barbara and Ogunniyi, Adesola and Olshan, Andrew and Press, Michael F and Rohde, Rebecca and Rybicki, Benjamin A and Babatunde Salako and Sanderson, Maureen and Shao, Yaming and David S Siscovick and Stanford, Janet L and Stevens, Victoria L and Stram, Alex and Strom, Sara S and Vaidya, Dhananjay and Witte, John S and Yao, Jie and Zhu, Xiaofeng and Ziegler, Regina G and Alan B Zonderman and Adeyemo, Adebowale and Ambs, Stefan and Cushman, Mary and Jessica Faul and Hakonarson, Hakon and Levin, Albert M and Nathanson, Katherine L and Erin B Ware and David R Weir and Zhao, Wei and Zhi, Degui and Donna K Arnett and Grant, Struan F A and Sharon L R Kardia and Oloapde, Olufunmilayo I and Rao, D C and Charles N Rotimi and Sale, Michele M and L Keoki Williams and Zemel, Babette S and Becker, Diane M and Ingrid B Borecki and Michele K Evans and Tamara B Harris and Hirschhorn, Joel N and Li, Yun and Patel, Sanjay R and Psaty, Bruce M and Rotter, Jerome I and Wilson, James G and Bowden, Donald W and Cupples, L Adrienne and Christopher A Haiman and Ruth J F Loos and Kari E North} } @article {9387, title = {Documentation of Blood-Based Biomarkers in the 2014 Health and Retirement Study}, year = {2017}, month = {12/2017}, institution = {Survey Research Center, Institute for Social Research, University of Michigan}, address = {Ann Arbor, MI}, author = {Eileen M. Crimmins and Jessica Faul and Jung K Kim and David R Weir} } @article {9429, title = {Gene-by-Psychosocial Factor Interactions Influence Diastolic Blood Pressure in European and African Ancestry Populations: Meta-Analysis of Four Cohort Studies.}, journal = {Int J Environ Res Public Health}, volume = {14}, year = {2017}, abstract = {Inter-individual variability in blood pressure (BP) is influenced by both genetic and non-genetic factors including socioeconomic and psychosocial stressors. A deeper understanding of the gene-by-socioeconomic/psychosocial factor interactions on BP may help to identify individuals that are genetically susceptible to high BP in specific social contexts. In this study, we used a genomic region-based method for longitudinal analysis, Longitudinal Gene-Environment-Wide Interaction Studies (LGEWIS), to evaluate the effects of interactions between known socioeconomic/psychosocial and genetic risk factors on systolic and diastolic BP in four large epidemiologic cohorts of European and/or African ancestry. After correction for multiple testing, two interactions were significantly associated with diastolic BP. In European ancestry participants, outward/trait anger score had a significant interaction with the C10orf107 genomic region (p = 0.0019). In African ancestry participants, depressive symptom score had a significant interaction with the HFE genomic region (p = 0.0048). This study provides a foundation for using genomic region-based longitudinal analysis to identify subgroups of the population that may be at greater risk of elevated BP due to the combined influence of genetic and socioeconomic/psychosocial risk factors.}, keywords = {Blood pressure, Genetics, GWAS, Meta-analyses, Psychosocial, Socioeconomic factors}, issn = {1660-4601}, doi = {10.3390/ijerph14121596}, author = {Wei Zhao and Yasutake, Kalyn and August, Carmella and Scott M Ratliff and Jessica Faul and Boerwinkle, Eric and Chakravarti, Aravinda and Ana V. Diez-Roux and Gao, Yan and Michael E Griswold and Gerardo Heiss and Sharon L R Kardia and Alanna C Morrison and Musani, Solomon K and Mwasongwe, Stanford and Kari E North and Rose, Kathryn M and Sims, Mario and Yan V Sun and David R Weir and Belinda L Needham} } @article {12131, title = {Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity.}, journal = {Nature Communications}, volume = {8}, year = {2017}, pages = {910}, abstract = {

Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents{\textquoteright} survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.

}, keywords = {Alleles, Body Mass Index, Coronary Disease, Education, Genetic Predisposition to Disease, Genome-Wide Association Study, HLA-DQ alpha-Chains, HLA-DRB1 Chains, Humans, Insulin Resistance, Life Style, Lipoprotein(a), Lipoproteins, HDL, Longevity, Lung Neoplasms, Obesity, Polymorphism, Single Nucleotide, Smoking, Socioeconomic factors}, issn = {2041-1723}, doi = {10.1038/s41467-017-00934-5}, author = {Joshi, Peter K and Nicola Pirastu and Kentistou, Katherine A and Fischer, Krista and Edith Hofer and Schraut, Katharina E and Clark, David W and Nutile, Teresa and Barnes, Catriona L K and Paul Rhj Timmers and Shen, Xia and Gandin, Ilaria and McDaid, Aaron F and Hansen, Thomas Folkmann and Gordon, Scott D and Giulianini, Franco and Boutin, Thibaud S and Abdellaoui, Abdel and Zhao, Wei and Medina-Gomez, Carolina and Traci M Bartz and Trompet, Stella and Leslie A Lange and Raffield, Laura and van der Spek, Ashley and Galesloot, Tessel E and Proitsi, Petroula and Yanek, Lisa R and Bielak, Lawrence F and Payton, Antony and Murgia, Federico and Concas, Maria Pina and Biino, Ginevra and Tajuddin, Salman M and Sepp{\"a}l{\"a}, Ilkka and Amin, Najaf and Boerwinkle, Eric and B{\o}rglum, Anders D and Campbell, Archie and Ellen W Demerath and Demuth, Ilja and Jessica Faul and Ford, Ian and Gialluisi, Alessandro and G{\"o}gele, Martin and Graff, Mariaelisa and Aroon Hingorani and Jouke-Jan Hottenga and Hougaard, David M and Hurme, Mikko A and Ikram, M Arfan and Jylh{\"a}, Marja and Kuh, Diana and Ligthart, Lannie and Lill, Christina M and Lindenberger, Ulman and Lumley, Thomas and M{\"a}gi, Reedik and Marques-Vidal, Pedro and Sarah E Medland and Lili Milani and Nagy, Reka and William E R Ollier and Peyser, Patricia A and Pramstaller, Peter P and Ridker, Paul M and Fernando Rivadeneira and Ruggiero, Daniela and Saba, Yasaman and Schmidt, Reinhold and Schmidt, Helena and Slagboom, P Eline and Smith, Blair H and Smith, Jennifer A and Sotoodehnia, Nona and Steinhagen-Thiessen, Elisabeth and van Rooij, Frank J A and Verbeek, Andr{\'e} L and Vermeulen, Sita H and Vollenweider, Peter and Wang, Yunpeng and Werge, Thomas and Whitfield, John B and Alan B Zonderman and Lehtim{\"a}ki, Terho and Michele K Evans and Pirastu, Mario and Fuchsberger, Christian and Bertram, Lars and Pendleton, Neil and Sharon L R Kardia and Ciullo, Marina and Becker, Diane M and Wong, Andrew and Psaty, Bruce M and Cornelia M van Duijn and Wilson, James G and Jukema, J Wouter and Lambertus A Kiemeney and Andr{\'e} G Uitterlinden and Franceschini, Nora and Kari E North and David R Weir and Andres Metspalu and Dorret I Boomsma and Caroline Hayward and Daniel I Chasman and Nicholas G Martin and Sattar, Naveed and Campbell, Harry and T{\~o}nu Esko and Kutalik, Zolt{\'a}n and James F Wilson} } @article {9048, title = {HRS Institutional Review Board Information}, year = {2017}, month = {10/2017}, institution = {Survey Research Center, Institute for Social Research, University of Michigan}, address = {Ann Arbor, MI}, author = {David R Weir} } @article {9066, title = {HRS Psychosocial and Lifestyle Questionnaire 2006-2016}, year = {2017}, institution = {Survey Research Center, Institute for Social Research, University of Michigan}, address = {Ann Arbor, Michigan}, author = {Jacqui Smith and Lindsay H Ryan and Gwenith G Fisher and Amanda Sonnega and David R Weir} } @article {9049, title = {Mortality selection in a genetic sample and implications for association studies.}, journal = {International Journal of Epidemiolpgy}, volume = {46}, year = {2017}, month = {08/2017}, abstract = {

Background: Mortality selection occurs when a non-random subset of a population of interest has died before data collection and is unobserved in the data. Mortality selection is of general concern in the social and health sciences, but has received little attention in genetic epidemiology. We tested the hypothesis that mortality selection may bias genetic association estimates, using data from the US-based Health and Retirement Study (HRS).

Methods: We tested mortality selection into the HRS genetic database by comparing HRS respondents who survive until genetic data collection in 2006 with those who do not. We next modelled mortality selection on demographic, health and social characteristics to calculate mortality selection probability weights. We analysed polygenic score associations with several traits before and after applying inverse-probability weighting to account for mortality selection. We tested simple associations and time-varying genetic associations (i.e. gene-by-cohort interactions).

Results: We observed mortality selection into the HRS genetic database on demographic, health and social characteristics. Correction for mortality selection using inverse probability weighting methods did not change simple association estimates. However, using these methods did change estimates of gene-by-cohort interaction effects. Correction for mortality selection changed gene-by-cohort interaction estimates in the opposite direction from increased mortality selection based on analysis of HRS respondents surviving through 2012.

Conclusions: Mortality selection may bias estimates of gene-by-cohort interaction effects. Analyses of HRS data can adjust for mortality selection associated with observables by including probability weights. Mortality selection is a potential confounder of genetic association studies, but the magnitude of confounding varies by trait.

}, keywords = {Genetics, GWAS, Mortality}, issn = {1464-3685}, doi = {10.1093/ije/dyx041}, author = {Benjamin W Domingue and Daniel W. Belsky and Harrati, Amal and Dalton C Conley and David R Weir and Jason D Boardman} } @article {9465, title = {The obesity paradox and incident cardiovascular disease: A population-based study.}, journal = {PLoS One}, volume = {12}, year = {2017}, month = {2017}, pages = {e0188636}, abstract = {

BACKGROUND: Prior work suggests that obesity may confer a survival advantage among persons with cardiovascular disease (CVD). This obesity "paradox" is frequently studied in the context of prevalent disease, a stage in the disease process when confounding from illness-related weight loss and selective survival are especially problematic. Our objective was to examine the association of obesity with mortality among persons with incident CVD, where biases are potentially reduced, and to compare these findings with those based on prevalent disease.

METHODS: We used data from the Health and Retirement Study, an ongoing, nationally representative longitudinal survey of U.S. adults age 50 years and older initiated in 1992 and linked to Medicare claims. Cox proportional hazard models were used to estimate the association between weight status and mortality among persons with specific CVD diagnoses. CVD diagnoses were established by self-reported survey data as well as Medicare claims. Prevalent disease models used concurrent weight status, and incident disease models used pre-diagnosis weight status.

RESULTS: We examined myocardial infarction, congestive heart failure, stroke, and ischemic heart disease. A strong and significant obesity paradox was consistently observed in prevalent disease models (hazard of death 18-36\% lower for obese class I relative to normal weight), replicating prior findings. However, in incident disease models of the same conditions in the same dataset, there was no evidence of this survival benefit. Findings from models using survey- vs. claims-based diagnoses were largely consistent.

CONCLUSION: We observed an obesity paradox in prevalent CVD, replicating prior findings in a population-based sample with longer-term follow-up. In incident CVD, however, we did not find evidence of a survival advantage for obesity. Our findings do not offer support for reevaluating clinical and public health guidelines in pursuit of a potential obesity paradox.

}, keywords = {BMI, Cardiovascular disease, Obesity}, issn = {1932-6203}, doi = {10.1371/journal.pone.0188636}, author = {Virginia W Chang and Kenneth M. Langa and David R Weir and Theodore J Iwashyna} } @article {12120, title = {Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations.}, journal = {PLoS Genetics}, volume = {13}, year = {2017}, pages = {e1006728}, abstract = {

Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25{\texttimes}10-8) for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one novel locus (FRMD3) for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension.

}, keywords = {African Americans, Animals, Basic Helix-Loop-Helix Transcription Factors, Blood pressure, Cadherins, Case-Control Studies, Female, Genetic Loci, Genome-Wide Association Study, Humans, Hypertension, Male, Membrane Proteins, Mice, Multifactorial Inheritance, Polymorphism, Single Nucleotide}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1006728}, author = {Liang, Jingjing and Le, Thu H and Digna R Velez Edwards and Bamidele O Tayo and Gaulton, Kyle J and Smith, Jennifer A and Lu, Yingchang and Jensen, Richard A and Chen, Guanjie and Yanek, Lisa R and Schwander, Karen and Tajuddin, Salman M and Sofer, Tamar and Kim, Wonji and Kayima, James and McKenzie, Colin A and Fox, Ervin and Michael A Nalls and Young, J Hunter and Yan V Sun and Lane, Jacqueline M and Cechova, Sylvia and Zhou, Jie and Tang, Hua and Myriam Fornage and Musani, Solomon K and Wang, Heming and Lee, Juyoung and Adeyemo, Adebowale and Dreisbach, Albert W and Forrester, Terrence and Chu, Pei-Lun and Anne Cappola and Michele K Evans and Alanna C Morrison and Martin, Lisa W and Kerri Wiggins and Hui, Qin and Zhao, Wei and Jackson, Rebecca D and Erin B Ware and Jessica Faul and Reiner, Alex P and Bray, Michael and Denny, Joshua C and Thomas H Mosley and Walter R Palmas and Guo, Xiuqing and George J Papanicolaou and Alan Penman and Polak, Joseph F and Kenneth Rice and Taylor, Ken D and Boerwinkle, Eric and Erwin P Bottinger and Liu, Kiang and Neil Risch and Hunt, Steven C and Charles Kooperberg and Alan B Zonderman and Laurie, Cathy C and Becker, Diane M and Cai, Jianwen and Ruth J F Loos and Psaty, Bruce M and David R Weir and Sharon L R Kardia and Donna K Arnett and Won, Sungho and Edwards, Todd L and Redline, Susan and Cooper, Richard S and Rao, D C and Rotter, Jerome I and Charles N Rotimi and Levy, Daniel and Chakravarti, Aravinda and Zhu, Xiaofeng and Franceschini, Nora} } @article {12133, title = {SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function.}, journal = {Journal of the American Society of Nephrology }, volume = {28}, year = {2017}, pages = {981-994}, abstract = {

Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (: 111,666; : 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea (, , and ; <3.7{\texttimes}10), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, (=5.4{\texttimes}10 by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of and -knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation.

}, keywords = {Animals, Exome, Genetic Loci, Genome-Wide Association Study, Glomerular Filtration Rate, Humans, kidney, Protein Tyrosine Phosphatases, Proto-Oncogene Proteins, Son of Sevenless Proteins, Zebrafish}, issn = {1533-3450}, doi = {10.1681/ASN.2016020131}, author = {Li, Man and Li, Yong and Weeks, Olivia and Mijatovic, Vladan and Teumer, Alexander and Huffman, Jennifer E and Tromp, Gerard and Fuchsberger, Christian and Gorski, Mathias and Lyytik{\"a}inen, Leo-Pekka and Nutile, Teresa and Sedaghat, Sanaz and Sorice, Rossella and Tin, Adrienne and Yang, Qiong and Ahluwalia, Tarunveer S and Dan E Arking and Bihlmeyer, Nathan A and B{\"o}ger, Carsten A and Carroll, Robert J and Daniel I Chasman and Marilyn C Cornelis and Dehghan, Abbas and Jessica Faul and Feitosa, Mary F and Gambaro, Giovanni and Paolo P. Gasparini and Giulianini, Franco and Iris M Heid and Huang, Jinyan and Imboden, Medea and Jackson, Anne U and Janina Jeff and Jhun, Min A and Katz, Ronit and Kifley, Annette and Kilpel{\"a}inen, Tuomas O and Kumar, Ashish and Laakso, Markku and Li-Gao, Ruifang and Kurt Lohman and Lu, Yingchang and M{\"a}gi, Reedik and Malerba, Giovanni and Mihailov, Evelin and Mohlke, Karen L and Dennis O Mook-Kanamori and Robino, Antonietta and Ruderfer, Douglas and Salvi, Erika and Schick, Ursula M and Schulz, Christina-Alexandra and Smith, Albert V and Smith, Jennifer A and Traglia, Michela and Laura M Yerges-Armstrong and Zhao, Wei and Goodarzi, Mark O and Kraja, Aldi T and Liu, Chunyu and Wessel, Jennifer and Boerwinkle, Eric and Ingrid B Borecki and Bork-Jensen, Jette and Erwin P Bottinger and Braga, Daniele and Brandslund, Ivan and Brody, Jennifer A and Campbell, Archie and Carey, David J and Cramer Christensen and Coresh, Josef and Crook, Errol and Curhan, Gary C and Cusi, Daniele and de Boer, Ian H and de Vries, Aiko P J and Denny, Joshua C and Devuyst, Olivier and Dreisbach, Albert W and Endlich, Karlhans and T{\~o}nu Esko and Franco, Oscar H and Fulop, Tibor and Gerhard, Glenn S and Gl{\"u}mer, Charlotte and Gottesman, Omri and Grarup, Niels and Gudnason, Vilmundur and Hansen, Torben and Tamara B Harris and Caroline Hayward and Lynne J Hocking and Hofman, Albert and Hu, Frank B and Husemoen, Lise Lotte N and Jackson, Rebecca D and J{\o}rgensen, Torben and J{\o}rgensen, Marit E and K{\"a}h{\"o}nen, Mika and Sharon L R Kardia and K{\"o}nig, Wolfgang and Charles Kooperberg and Kriebel, Jennifer and Lenore J Launer and Lauritzen, Torsten and Lehtim{\"a}ki, Terho and Levy, Daniel and Linksted, Pamela and Linneberg, Allan and Liu, Yongmei and Ruth J F Loos and Lupo, Antonio and Meisinger, Christine and Melander, Olle and Andres Metspalu and Mitchell, Paul and Nauck, Matthias and N{\"u}rnberg, Peter and Orho-Melander, Marju and Parsa, Afshin and Pedersen, Oluf and Peters, Annette and Peters, Ulrike and Polasek, Ozren and David J Porteous and Nicole M Probst-Hensch and Psaty, Bruce M and Qi, Lu and Olli T Raitakari and Reiner, Alex P and Rettig, Rainer and Ridker, Paul M and Fernando Rivadeneira and Rossouw, Jacques E and Schmidt, Frank and David S Siscovick and Soranzo, Nicole and Strauch, Konstantin and Toniolo, Daniela and Stephen T Turner and Andr{\'e} G Uitterlinden and Ulivi, Sheila and Velayutham, Dinesh and V{\"o}lker, Uwe and V{\"o}lzke, Henry and Waldenberger, Melanie and Wang, Jie Jin and David R Weir and Daniel Witte and Kuivaniemi, Helena and Caroline S Fox and Franceschini, Nora and Goessling, Wolfram and K{\"o}ttgen, Anna and Chu, Audrey Y} } @article {9065, title = {Venous Blood Collection and Assay Protocol in the 2016 Health and Retirement Study}, year = {2017}, institution = {Survey Research Center, Institute for Social Research, University of Michigan}, address = {Ann Arbor, Michigan}, author = {Eileen M. Crimmins and Jessica Faul and Bharat Thyagarajan and David R Weir} } @article {9950, title = {2016 Harmonized Cognitive Assessment Protocol (HCAP) Study Protocol Summary}, year = {2016}, month = {03/2018}, pages = {1-15}, institution = {Health and Retirement Study, Survey Research Center, Institute for Social Research, University of Michigan}, address = {Ann Arbor, MI}, author = {David R Weir and Kenneth M. Langa and Lindsay H Ryan} } @article {8974, title = {Cohort Changes in Social Security Benefits and Pension Wealth}, number = {WP 2016-350}, year = {2016}, institution = {University of Michigan}, address = {Ann Arbor, MI}, url = {http://www.mrrc.isr.umich.edu/publications/papers/pdf/wp350.pdf}, author = {Fang, Chichun and Charles Brown and David R Weir} } @article {9314, title = {Evaluating Strategies for Reducing Field Costs in a Longitudinal Study}, year = {2016}, month = {06/2017}, pages = {1-8}, institution = {Institute for Social Research, University of Michigan}, address = {Ann Arbor, MI}, author = {David R Weir and Mary Beth Ofstedal} } @article {8618, title = {Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses.}, journal = {Nat Genet}, volume = {48}, year = {2016}, month = {2016 06}, pages = {624-33}, abstract = {

Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.

}, keywords = {Anxiety Disorders, Bayes Theorem, depression, Genome-Wide Association Study, Humans, Neuroticism, Phenotype, Polymorphism, Single Nucleotide}, issn = {1546-1718}, doi = {10.1038/ng.3552}, author = {Okbay, Aysu and Baselmans, Bart M L and De Neve, Jan-Emmanuel and Turley, Patrick and Nivard, Michel G and Mark Alan Fontana and Meddens, S Fleur W and Richard Karlsson Linn{\'e}r and Cornelius A Rietveld and Derringer, Jaime and Gratten, Jacob and Lee, James J and Liu, Jimmy Z and de Vlaming, Ronald and Ahluwalia, Tarunveer S and Buchwald, Jadwiga and Cavadino, Alana and Frazier-Wood, Alexis C and Furlotte, Nicholas A and Garfield, Victoria and Geisel, Marie Henrike and Gonzalez, Juan R and Haitjema, Saskia and Karlsson, Robert and van der Laan, Sander W and Ladwig, Karl-Heinz and J. Lahti and Sven J van der Lee and Penelope A Lind and Tian Liu and Lindsay K Matteson and Mihailov, Evelin and Michael B Miller and Minica, Camelia C and Ilja M Nolte and Dennis O Mook-Kanamori and van der Most, Peter J and Christopher J Oldmeadow and Qian, Yong and Olli T Raitakari and Rawal, Rajesh and Realo, Anu and Rueedi, Rico and Schmidt, B{\"o}rge and Albert Vernon Smith and Stergiakouli, Evie and Toshiko Tanaka and Kent D Taylor and Wedenoja, Juho and J{\"u}rgen Wellmann and Westra, Harm-Jan and Willems, Sara M and Wei Zhao and Amin, Najaf and Bakshi, Andrew and Patricia A. Boyle and Cherney, Samantha and Cox, Simon R and Gail Davies and Davis, Oliver S P and Ding, Jun and Nese Direk and Eibich, Peter and Emeny, Rebecca T and Fatemifar, Ghazaleh and Jessica Faul and Luigi Ferrucci and Andreas J Forstner and Gieger, Christian and Gupta, Richa and Tamara B Harris and Harris, Juliette M and Holliday, Elizabeth G and Jouke-Jan Hottenga and Philip L de Jager and Marika A Kaakinen and Kajantie, Eero and Karhunen, Ville and Kolcic, Ivana and Kumari, Meena and Lenore J Launer and Lude L Franke and Li-Gao, Ruifang and Koini, Marisa and Loukola, Anu and Marques-Vidal, Pedro and Grant W Montgomery and Mosing, Miriam A and Paternoster, Lavinia and Pattie, Alison and Katja E Petrovic and Pulkki-Raback, Laura and Quaye, Lydia and Katri R{\"a}ikk{\"o}nen and Rudan, Igor and Rodney J Scott and Jennifer A Smith and Angelina R Sutin and Trzaskowski, Maciej and Anna A E Vinkhuyzen and Lei Yu and Zabaneh, Delilah and John R. Attia and David A Bennett and Klaus Berger and Bertram, Lars and Dorret I Boomsma and Snieder, Harold and Chang, Shun-Chiao and Francesco Cucca and Ian J Deary and Cornelia M van Duijn and Johan G Eriksson and B{\"u}ltmann, Ute and Eco J. C. de Geus and Groenen, Patrick J F and Gudnason, Vilmundur and Hansen, Torben and Catharina A Hartman and Haworth, Claire M A and Caroline Hayward and Andrew C Heath and Hinds, David A and Hypp{\"o}nen, Elina and Iacono, William G and J{\"a}rvelin, Marjo-Riitta and J{\"o}ckel, Karl-Heinz and Kaprio, Jaakko and Sharon L R Kardia and Keltikangas-J{\"a}rvinen, Liisa and Kraft, Peter and Laura D Kubzansky and Lehtim{\"a}ki, Terho and Patrik K E Magnusson and Nicholas G Martin and McGue, Matt and Andres Metspalu and Melinda C Mills and de Mutsert, Ren{\'e}e and Oldehinkel, Albertine J and Pasterkamp, Gerard and Nancy L Pedersen and Plomin, Robert and Polasek, Ozren and Power, Christine and Rich, Stephen S and Rosendaal, Frits R and Hester M. den Ruijter and Schlessinger, David and Schmidt, Helena and Svento, Rauli and Schmidt, Reinhold and Alizadeh, Behrooz Z and Thorkild I. A. S{\o}rensen and Timothy Spector and Andrew Steptoe and Antonio Terracciano and A. Roy Thurik and Nicholas J Timpson and Henning Tiemeier and Andr{\'e} G Uitterlinden and Vollenweider, Peter and Wagner, Gert G and David R Weir and Yang, Jian and Dalton C Conley and Hofman, Albert and Johannesson, Magnus and David I Laibson and Sarah E Medland and Meyer, Michelle N and Pickrell, Joseph K and T{\~o}nu Esko and Krueger, Robert F and Jonathan P. Beauchamp and Philipp D Koellinger and Daniel J. Benjamin and Bartels, Meike and Cesarini, David} } @article {8881, title = {Genome-wide analysis identifies 12 loci influencing human reproductive behavior.}, journal = {Nat Genet}, volume = {48}, year = {2016}, month = {2016 Dec}, pages = {1462-1472}, abstract = {

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits.

}, issn = {1546-1718}, doi = {10.1038/ng.3698}, author = {Nicola Barban and Jansen, Rick and de Vlaming, Ronald and Vaez, Ahmad and Mandemakers, Jornt J and Felix C Tropf and Shen, Xia and James F Wilson and Daniel I Chasman and Ilja M Nolte and Tragante, Vinicius and van der Laan, Sander W and Perry, John R B and Kong, Augustine and Ahluwalia, Tarunveer S and Albrecht, Eva and Laura M Yerges-Armstrong and Atzmon, Gil and Auro, Kirsi and Kristin L. Ayers and Bakshi, Andrew and Ben-Avraham, Danny and Klaus Berger and Bergman, Aviv and Bertram, Lars and Bielak, Lawrence F and Bjornsdottir, Gyda and Bonder, Marc Jan and Broer, Linda and Bui, Minh and Barbieri, Caterina and Cavadino, Alana and Chavarro, Jorge E and Turman, Constance and Maria Pina Concas and Cordell, Heather J and Gail Davies and Eibich, Peter and Eriksson, Nicholas and T{\~o}nu Esko and Eriksson, Joel and Falahi, Fahimeh and Felix, Janine F and Mark Alan Fontana and Lude L Franke and Gandin, Ilaria and Gaskins, Audrey J and Gieger, Christian and Gunderson, Erica P and Guo, Xiuqing and Caroline Hayward and He, Chunyan and Edith Hofer and Huang, Hongyan and Joshi, Peter K and Kanoni, Stavroula and Karlsson, Robert and Kiechl, Stefan and Kifley, Annette and Kluttig, Alexander and Kraft, Peter and Lagou, Vasiliki and Lecoeur, Cecile and Lahti, Jari and Li-Gao, Ruifang and Penelope A Lind and Tian Liu and Makalic, Enes and Mamasoula, Crysovalanto and Lindsay K Matteson and Mbarek, Hamdi and McArdle, Patrick F and McMahon, George and Meddens, S Fleur W and Mihailov, Evelin and Michael B Miller and Missmer, Stacey A and Monnereau, Claire and van der Most, Peter J and Myhre, Ronny and Michael A Nalls and Nutile, Teresa and Ioanna Panagiota Kalafati and Porcu, Eleonora and Prokopenko, Inga and Rajan, Kumar B and Rich-Edwards, Janet and Cornelius A Rietveld and Robino, Antonietta and Rose, Lynda M and Rueedi, Rico and Ryan, Kathleen A and Saba, Yasaman and Schmidt, Daniel and Jennifer A Smith and Stolk, Lisette and Streeten, Elizabeth and T{\"o}njes, Anke and Thorleifsson, Gudmar and Ulivi, Sheila and Wedenoja, Juho and J{\"u}rgen Wellmann and Willeit, Peter and Yao, Jie and Yengo, Loic and Jing Hua Zhao and Wei Zhao and Zhernakova, Daria V and Amin, Najaf and Andrews, Howard and Balkau, Beverley and Barzilai, Nir and Bergmann, Sven and Biino, Ginevra and Bisgaard, Hans and B{\o}nnelykke, Klaus and Dorret I Boomsma and Buring, Julie E and Campbell, Harry and Cappellani, Stefania and Ciullo, Marina and Cox, Simon R and Francesco Cucca and Toniolo, Daniela and Davey-Smith, George and Ian J Deary and George Dedoussis and Deloukas, Panos and Cornelia M van Duijn and Eco J. C. de Geus and Johan G Eriksson and Jessica Faul and Cinzia Felicita Sala and Froguel, Philippe and Paolo P. Gasparini and Giorgia G Girotto and Hans-J{\"o}rgen Grabe and Greiser, Karin Halina and Groenen, Patrick J F and de Haan, Hugoline G and Haerting, Johannes and Tamara B Harris and Andrew C Heath and Heikkil{\"a}, Kauko and Hofman, Albert and Homuth, Georg and Holliday, Elizabeth G and John L Hopper and Hypp{\"o}nen, Elina and Jacobsson, Bo and Vincent Jaddoe and Johannesson, Magnus and Jugessur, Astanand and K{\"a}h{\"o}nen, Mika and Kajantie, Eero and Sharon L R Kardia and Keavney, Bernard and Kolcic, Ivana and Koponen, P{\"a}ivikki and Kovacs, Peter and Kronenberg, Florian and Kutalik, Zolt{\'a}n and La Bianca, Martina and Lachance, Genevieve and Iacono, William G and Lai, Sandra and Lehtim{\"a}ki, Terho and David C Liewald and Lindgren, Cecilia M and Yongmei Liu and Luben, Robert and Lucht, Michael and Luoto, Riitta and Magnus, Per and Patrik K E Magnusson and Nicholas G Martin and McGue, Matt and McQuillan, Ruth and Sarah E Medland and Meisinger, Christa and Mellstr{\"o}m, Dan and Andres Metspalu and Traglia, Michela and Lili Milani and Mitchell, Paul and Grant W Montgomery and Dennis O Mook-Kanamori and de Mutsert, Ren{\'e}e and Nohr, Ellen A and Ohlsson, Claes and Olsen, J{\o}rn and Ong, Ken K and Paternoster, Lavinia and Pattie, Alison and Brenda W J H Penninx and Markus Perola and Peyser, Patricia A and Pirastu, Mario and Polasek, Ozren and Power, Chris and Kaprio, Jaakko and Raffel, Leslie J and Katri R{\"a}ikk{\"o}nen and Olli T Raitakari and Ridker, Paul M and Ring, Susan M and Roll, Kathryn and Rudan, Igor and Ruggiero, Daniela and Rujescu, Dan and Veikko Salomaa and Schlessinger, David and Schmidt, Helena and Schmidt, Reinhold and Schupf, Nicole and Johannes H Smit and Sorice, Rossella and Timothy Spector and John M Starr and St{\"o}ckl, Doris and Strauch, Konstantin and Stumvoll, Michael and Swertz, Morris A and Thorsteinsdottir, Unnur and A. Roy Thurik and Nicholas J Timpson and Tung, Joyce Y and Andr{\'e} G Uitterlinden and Vaccargiu, Simona and Viikari, Jorma and Vitart, Veronique and V{\"o}lzke, Henry and Vollenweider, Peter and Vuckovic, Dragana and Waage, Johannes and Wagner, Gert G and Wang, Jie Jin and Wareham, Nicholas J and David R Weir and Gonneke Willemsen and Willeit, Johann and Alan F Wright and Krina T Zondervan and Stefansson, Kari and Krueger, Robert F and Lee, James J and Daniel J. Benjamin and Cesarini, David and Philipp D Koellinger and den Hoed, Marcel and Snieder, Harold and Melinda C Mills} } @article {8607, title = {GENOME-WIDE ASSOCIATION STUDY (GWAS) AND GENOME-WIDE BY ENVIRONMENT INTERACTION STUDY (GWEIS) OF DEPRESSIVE SYMPTOMS IN AFRICAN AMERICAN AND HISPANIC/LATINA WOMEN.}, journal = {Depress Anxiety}, volume = {33}, year = {2016}, month = {2016 Apr}, pages = {265-80}, abstract = {

BACKGROUND: Genome-wide association studies (GWAS) have made little progress in identifying variants linked to depression. We hypothesized that examining depressive symptoms and considering gene-environment interaction (GxE) might improve efficiency for gene discovery. We therefore conducted a GWAS and genome-wide by environment interaction study (GWEIS) of depressive symptoms.

METHODS: Using data from the SHARe cohort of the Women{\textquoteright}s Health Initiative, comprising African Americans (n = 7,179) and Hispanics/Latinas (n = 3,138), we examined genetic main effects and GxE with stressful life events and social support. We also conducted a heritability analysis using genome-wide complex trait analysis (GCTA). Replication was attempted in four independent cohorts.

RESULTS: No SNPs achieved genome-wide significance for main effects in either discovery sample. The top signals in African Americans were rs73531535 (located 20 kb from GPR139, P = 5.75 {\texttimes} 10(-8) ) and rs75407252 (intronic to CACNA2D3, P = 6.99 {\texttimes} 10(-7) ). In Hispanics/Latinas, the top signals were rs2532087 (located 27 kb from CD38, P = 2.44 {\texttimes} 10(-7) ) and rs4542757 (intronic to DCC, P = 7.31 {\texttimes} 10(-7) ). In the GEWIS with stressful life events, one interaction signal was genome-wide significant in African Americans (rs4652467; P = 4.10 {\texttimes} 10(-10) ; located 14 kb from CEP350). This interaction was not observed in a smaller replication cohort. Although heritability estimates for depressive symptoms and stressful life events were each less than 10\%, they were strongly genetically correlated (rG = 0.95), suggesting that common variation underlying self-reported depressive symptoms and stressful life event exposure, though modest on their own, were highly overlapping in this sample.

CONCLUSIONS: Our results underscore the need for larger samples, more GEWIS, and greater investigation into genetic and environmental determinants of depressive symptoms in minorities.

}, keywords = {African Americans, Aged, depression, Female, Gene-Environment Interaction, Genome-Wide Association Study, Hispanic Americans, Humans, Life Change Events, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Risk Factors, Self Report}, issn = {1520-6394}, doi = {10.1002/da.22484}, author = {Dunn, Erin C and Wiste, Anna and Radmanesh, Farid and Almli, Lynn M and Gogarten, Stephanie M and Sofer, Tamar and Jessica Faul and Sharon L R Kardia and Jennifer A Smith and David R Weir and Wei Zhao and Soare, Thomas W and Saira S Mirza and Karin Hek and Henning Tiemeier and Goveas, Joseph S and Sarto, Gloria E and Snively, Beverly M and Marilyn C Cornelis and Karestan C Koenen and Kraft, Peter and Shaun M Purcell and Ressler, Kerry J and Rosand, Jonathan and Wassertheil-Smoller, Sylvia and Smoller, Jordan W} } @article {8883, title = {Genome-wide association study identifies 74 loci associated with educational attainment.}, journal = {Nature}, volume = {533}, year = {2016}, month = {2016 05 26}, pages = {539-42}, abstract = {

Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20\% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.

}, keywords = {Alzheimer{\textquoteright}s disease, Bipolar Disorder, Cognitive Ability, Education, Fetus, Genome-Wide Association Study, Humans, Molecular Sequence Annotation, Polymorphism, Single Nucleotide, Schizophrenia, United Kingdom}, issn = {1476-4687}, doi = {10.1038/nature17671}, author = {Okbay, Aysu and Jonathan P. Beauchamp and Mark Alan Fontana and Lee, James J and Pers, Tune H and Cornelius A Rietveld and Turley, Patrick and Chen, Guo-Bo and Emilsson, Valur and Meddens, S Fleur W and Oskarsson, Sven and Pickrell, Joseph K and Thom, Kevin and Pascal N Timshel and de Vlaming, Ronald and Abdel Abdellaoui and Ahluwalia, Tarunveer S and Bacelis, Jonas and Baumbach, Clemens and Bjornsdottir, Gyda and Brandsma, Johannes H and Maria Pina Concas and Derringer, Jaime and Furlotte, Nicholas A and Galesloot, Tessel E and Giorgia G Girotto and Gupta, Richa and Hall, Leanne M and Sarah E Harris and Edith Hofer and Horikoshi, Momoko and Huffman, Jennifer E and Kaasik, Kadri and Ioanna Panagiota Kalafati and Karlsson, Robert and Kong, Augustine and Lahti, Jari and Sven J van der Lee and Christiaan de Leeuw and Penelope A Lind and Lindgren, Karl-Oskar and Tian Liu and Mangino, Massimo and Marten, Jonathan and Mihailov, Evelin and Michael B Miller and van der Most, Peter J and Christopher J Oldmeadow and Payton, Antony and Pervjakova, Natalia and Wouter J Peyrot and Qian, Yong and Olli T Raitakari and Rueedi, Rico and Salvi, Erika and Schmidt, B{\"o}rge and Schraut, Katharina E and Jianxin Shi and Albert Vernon Smith and Poot, Raymond A and St Pourcain, Beate and Teumer, Alexander and Thorleifsson, Gudmar and Verweij, Niek and Vuckovic, Dragana and J{\"u}rgen Wellmann and Westra, Harm-Jan and Yang, Jingyun and Wei Zhao and Zhihong Zhu and Alizadeh, Behrooz Z and Amin, Najaf and Bakshi, Andrew and Baumeister, Sebastian E and Biino, Ginevra and B{\o}nnelykke, Klaus and Patricia A. Boyle and Campbell, Harry and Cappuccio, Francesco P and Gail Davies and De Neve, Jan-Emmanuel and Deloukas, Panos and Demuth, Ilja and Ding, Jun and Eibich, Peter and Eisele, Lewin and Eklund, Niina and Jessica Faul and Feitosa, Mary F and Andreas J Forstner and Gandin, Ilaria and Gunnarsson, Bjarni and Halld{\'o}rsson, Bjarni V and Tamara B Harris and Andrew C Heath and Lynne J Hocking and Holliday, Elizabeth G and Homuth, Georg and Horan, Michael A and Jouke-Jan Hottenga and Philip L de Jager and Joshi, Peter K and Jugessur, Astanand and Marika A Kaakinen and K{\"a}h{\"o}nen, Mika and Kanoni, Stavroula and Keltigangas-J{\"a}rvinen, Liisa and Lambertus A Kiemeney and Kolcic, Ivana and Koskinen, Seppo and Kraja, Aldi T and Kroh, Martin and Kutalik, Zolt{\'a}n and Latvala, Antti and Lenore J Launer and Lebreton, Ma{\"e}l P and Douglas F Levinson and Paul Lichtenstein and Lichtner, Peter and David C Liewald and Loukola, Anu and Pamela A F Madden and M{\"a}gi, Reedik and M{\"a}ki-Opas, Tomi and Riccardo E Marioni and Marques-Vidal, Pedro and Meddens, Gerardus A and McMahon, George and Meisinger, Christa and Meitinger, Thomas and Milaneschi, Yusplitri and Lili Milani and Grant W Montgomery and Myhre, Ronny and Nelson, Christopher P and Nyholt, Dale R and William E R Ollier and Aarno Palotie and Paternoster, Lavinia and Nancy L Pedersen and Katja E Petrovic and David J Porteous and Katri R{\"a}ikk{\"o}nen and Ring, Susan M and Robino, Antonietta and Rostapshova, Olga and Rudan, Igor and Rustichini, Aldo and Veikko Salomaa and Sanders, Alan R and Sarin, Antti-Pekka and Schmidt, Helena and Rodney J Scott and Smith, Blair H and Jennifer A Smith and Staessen, Jan A and Steinhagen-Thiessen, Elisabeth and Strauch, Konstantin and Antonio Terracciano and Tobin, Martin D and Ulivi, Sheila and Vaccargiu, Simona and Quaye, Lydia and van Rooij, Frank J A and Venturini, Cristina and Anna A E Vinkhuyzen and V{\"o}lker, Uwe and V{\"o}lzke, Henry and Vonk, Judith M and Vozzi, Diego and Waage, Johannes and Erin B Ware and Gonneke Willemsen and John R. Attia and David A Bennett and Klaus Berger and Bertram, Lars and Bisgaard, Hans and Dorret I Boomsma and Ingrid B Borecki and B{\"u}ltmann, Ute and Chabris, Christopher F and Francesco Cucca and Cusi, Daniele and Ian J Deary and George Dedoussis and Cornelia M van Duijn and Johan G Eriksson and Franke, Barbara and Lude L Franke and Paolo P. Gasparini and Gejman, Pablo V and Gieger, Christian and Hans-J{\"o}rgen Grabe and Gratten, Jacob and Groenen, Patrick J F and Gudnason, Vilmundur and van der Harst, Pim and Caroline Hayward and Hinds, David A and Hoffmann, Wolfgang and Hypp{\"o}nen, Elina and Iacono, William G and Jacobsson, Bo and J{\"a}rvelin, Marjo-Riitta and J{\"o}ckel, Karl-Heinz and Kaprio, Jaakko and Sharon L R Kardia and Lehtim{\"a}ki, Terho and Lehrer, Steven F and Patrik K E Magnusson and Nicholas G Martin and McGue, Matt and Andres Metspalu and Pendleton, Neil and Brenda W J H Penninx and Markus Perola and Nicola Pirastu and Pirastu, Mario and Polasek, Ozren and Posthuma, Danielle and Power, Christine and Province, Michael A and Nilesh J Samani and Schlessinger, David and Schmidt, Reinhold and Thorkild I. A. S{\o}rensen and Timothy Spector and Stefansson, Kari and Thorsteinsdottir, Unnur and A. Roy Thurik and Nicholas J Timpson and Henning Tiemeier and Tung, Joyce Y and Andr{\'e} G Uitterlinden and Vitart, Veronique and Vollenweider, Peter and David R Weir and James F Wilson and Alan F Wright and Dalton C Conley and Krueger, Robert F and George Davey Smith and Hofman, Albert and David I Laibson and Sarah E Medland and Meyer, Michelle N and Yang, Jian and Johannesson, Magnus and Peter M Visscher and T{\~o}nu Esko and Philipp D Koellinger and Cesarini, David and Daniel J. Benjamin} } @article {8614, title = {GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium.}, journal = {Aging Cell}, volume = {15}, year = {2016}, month = {2016 10}, pages = {792-800}, abstract = {

Decline in muscle strength with aging is an important predictor of health trajectory in the elderly. Several factors, including genetics, are proposed contributors to variability in muscle strength. To identify genetic contributors to muscle strength, a meta-analysis of genomewide association studies of handgrip was conducted. Grip strength was measured using a handheld dynamometer in 27~581 individuals of European descent over 65~years of age from 14 cohort studies. Genomewide association analysis was conducted on ~2.7 million imputed and genotyped variants (SNPs). Replication of the most significant findings was conducted using data from 6393 individuals from three cohorts. GWAS of lower body strength was also characterized in a subset of cohorts. Two genomewide significant (P-value< 5~{\texttimes}~10(-8) ) and 39 suggestive (P-value< 5~{\texttimes}~10(-5) ) associations were observed from meta-analysis of the discovery cohorts. After meta-analysis with replication cohorts, genomewide significant association was observed for rs752045 on chromosome 8 (β~=~0.47, SE~=~0.08, P-value~=~5.20~{\texttimes}~10(-10) ). This SNP is mapped to an intergenic region and is located within an accessible chromatin region (DNase hypersensitivity site) in skeletal muscle myotubes differentiated from the human skeletal muscle myoblasts cell line. This locus alters a binding motif of the CCAAT/enhancer-binding protein-β (CEBPB) that is implicated in muscle repair mechanisms. GWAS of lower body strength did not yield significant results. A common genetic variant in a chromosomal region that regulates myotube differentiation and muscle repair may contribute to variability in grip strength in the elderly. Further studies are needed to uncover the mechanisms that link this genetic variant with muscle strength.

}, keywords = {Adult, Aged, Chromatin Immunoprecipitation, Cohort Studies, Epigenesis, Genetic, Genome-Wide Association Study, Hand Strength, Humans, Molecular Sequence Annotation, Muscle Strength, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Reproducibility of Results}, issn = {1474-9726}, doi = {10.1111/acel.12468}, author = {Amy M Matteini and Toshiko Tanaka and Karasik, David and Atzmon, Gil and Chou, Wen-Chi and John D Eicher and Andrew D Johnson and Alice M. Arnold and Michele L Callisaya and Gail Davies and Daniel S Evans and Holtfreter, Birte and Kurt Lohman and Kathryn L Lunetta and Mangino, Massimo and Albert Vernon Smith and Jennifer A Smith and Teumer, Alexander and Lei Yu and Dan E Arking and Aron S Buchman and Chibinik, Lori B and Philip L de Jager and Jessica Faul and Melissa E Garcia and Gillham-Nasenya, Irina and Gudnason, Vilmundur and Hofman, Albert and Hsu, Yi-Hsiang and Ittermann, Till and Lahousse, Lies and David C Liewald and Yongmei Liu and Lopez, Lorna and Fernando Rivadeneira and Rotter, Jerome I and Siggeirsdottir, Kristin and John M Starr and Thomson, Russell and Tranah, Gregory J and Andr{\'e} G Uitterlinden and V{\"o}lker, Uwe and V{\"o}lzke, Henry and David R Weir and Kristine Yaffe and Wei Zhao and Wei Vivian Zhuang and Zmuda, Joseph M and David A Bennett and Steven R Cummings and Ian J Deary and Luigi Ferrucci and Tamara B Harris and Sharon L R Kardia and Kocher, Thomas and Stephen B Kritchevsky and Psaty, Bruce M and Seshadri, Sudha and Timothy Spector and Velandai K Srikanth and Beverly G Windham and Zillikens, M Carola and Anne B Newman and Jeremy D Walston and Douglas P Kiel and Joanne M Murabito} } @article {8704, title = {Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study.}, journal = {Proc Natl Acad Sci U S A}, volume = {113}, year = {2016}, month = {2016 10 18}, pages = {E6335-E6342}, abstract = {

Stress over the lifespan is thought to promote accelerated aging and early disease. Telomere length is a marker of cell aging that appears to be one mediator of this relationship. Telomere length is associated with early adversity and with chronic stressors in adulthood in many studies. Although cumulative lifespan adversity should have bigger impacts than single events, it is also possible that adversity in childhood has larger effects on later life health than adult stressors, as suggested by models of biological embedding in early life. No studies have examined the individual vs. cumulative effects of childhood and adulthood adversities on adult telomere length. Here, we examined the relationship between cumulative childhood and adulthood adversity, adding up a range of severe financial, traumatic, and social exposures, as well as comparing them to each other, in relation to salivary telomere length. We examined 4,598 men and women from the US Health and Retirement Study. Single adversities tended to have nonsignificant relations with telomere length. In adjusted models, lifetime cumulative adversity predicted 6\% greater odds of shorter telomere length. This result was mainly due to childhood adversity. In adjusted models for cumulative childhood adversity, the occurrence of each additional childhood event predicted 11\% increased odds of having short telomeres. This result appeared mainly because of social/traumatic exposures rather than financial exposures. This study suggests that the shadow of childhood adversity may reach far into later adulthood in part through cellular aging.

}, keywords = {Aged, Aged, 80 and over, Cellular Senescence, Female, Humans, Longevity, Male, Middle Aged, Multivariate Analysis, Odds Ratio, Public Health Surveillance, Risk Factors, Stress, Psychological, Telomere, Telomere Shortening, United States}, issn = {1091-6490}, doi = {10.1073/pnas.1525602113}, url = {http://www.pnas.org/content/113/42/E6335.long}, author = {Puterman, Eli and Gemmill, Alison and Karasek, Deborah and David R Weir and Nancy E Adler and Aric A Prather and Elissa S Epel} } @article {8885, title = {Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci.}, journal = {Nat Genet}, volume = {48}, year = {2016}, month = {2016 Oct}, pages = {1162-70}, abstract = {

Meta-analyses of association results for blood pressure using exome-centric single-variant and gene-based tests identified 31 new loci in a discovery stage among 146,562 individuals, with follow-up and meta-analysis in 180,726 additional individuals (total n = 327,288). These blood pressure-associated loci are enriched for known variants for cardiometabolic traits. Associations were also observed for the aggregation of rare and low-frequency missense variants in three genes, NPR1, DBH, and PTPMT1. In addition, blood pressure associations at 39 previously reported loci were confirmed. The identified variants implicate biological pathways related to cardiometabolic traits, vascular function, and development. Several new variants are inferred to have roles in transcription or as hubs in protein-protein interaction networks. Genetic risk scores constructed from the identified variants were strongly associated with coronary disease and myocardial infarction. This large collection of blood pressure-associated loci suggests new therapeutic strategies for hypertension, emphasizing a link with cardiometabolic risk.

}, issn = {1546-1718}, doi = {10.1038/ng.3660}, author = {Liu, Chunyu and Kraja, Aldi T and Jennifer A Smith and Brody, Jennifer A and Franceschini, Nora and Joshua C. Bis and Kenneth Rice and Alanna C Morrison and Lu, Yingchang and Weiss, Stefan and Guo, Xiuqing and Walter R Palmas and Martin, Lisa W and Yii-Der I Chen and Surendran, Praveen and Drenos, Fotios and Cook, James P and Auer, Paul L and Chu, Audrey Y and Giri, Ayush and Wei Zhao and Jakobsdottir, Johanna and Lin, Li-An and Stafford, Jeanette M and Amin, Najaf and Mei, Hao and Yao, Jie and Voorman, Arend and Larson, Martin G and Grove, Megan L and Albert Vernon Smith and Hwang, Shih-Jen and Chen, Han and Huan, Tianxiao and Kosova, Gulum and Stitziel, Nathan O and Kathiresan, Sekar and Nilesh J Samani and Schunkert, Heribert and Deloukas, Panos and Li, Man and Fuchsberger, Christian and Pattaro, Cristian and Gorski, Mathias and Charles Kooperberg and George J Papanicolaou and Rossouw, Jacques E and Jessica Faul and Sharon L R Kardia and Bouchard, Claude and Raffel, Leslie J and Andr{\'e} G Uitterlinden and Franco, Oscar H and Ramachandran S Vasan and O{\textquoteright}Donnell, Christopher J and Kent D Taylor and Liu, Kiang and Erwin P Bottinger and Gottesman, Omri and Daw, E Warwick and Giulianini, Franco and Ganesh, Santhi and Salfati, Elias and Tamara B Harris and Lenore J Launer and D{\"o}rr, Marcus and Felix, Stephan B and Rettig, Rainer and V{\"o}lzke, Henry and Eric S Kim and Lee, Wen-Jane and Lee, I-Te and Sheu, Wayne H-H and Tsosie, Krystal S and Digna R Velez Edwards and Yongmei Liu and Correa, Adolfo and David R Weir and V{\"o}lker, Uwe and Ridker, Paul M and Boerwinkle, Eric and Gudnason, Vilmundur and Reiner, Alexander P and Cornelia M van Duijn and Ingrid B Borecki and Edwards, Todd L and Chakravarti, Aravinda and Rotter, Jerome I and Psaty, Bruce M and Ruth J F Loos and Myriam Fornage and Georg B Ehret and Newton-Cheh, Christopher and Levy, Daniel and Daniel I Chasman} } @article {8534, title = {Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies.}, journal = {Psychol Med}, volume = {46}, year = {2016}, month = {2016 06}, pages = {1613-23}, abstract = {

BACKGROUND: Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains.

METHOD: We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons).

RESULTS: One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 {\texttimes} 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 {\texttimes} 10-6) with evidence of heterogeneity.

CONCLUSIONS: Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.

}, keywords = {depression, Depressive Disorder, Major, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Receptor, Melatonin, MT1, Somatoform Disorders}, issn = {1469-8978}, doi = {10.1017/S0033291715002081}, url = {https://www.ncbi.nlm.nih.gov/pubmed/26997408}, author = {Demirkan, A and J. Lahti and Nese Direk and Viktorin, A. and Kathryn L Lunetta and Antonio Terracciano and Michael A Nalls and Toshiko Tanaka and Karin Hek and Myriam Fornage and J{\"u}rgen Wellmann and Marilyn C Cornelis and Ollila, H. M. and Lei Yu and Luke C Pilling and Isaacs, A and Aarno Palotie and Wei Vivian Zhuang and Alan B Zonderman and Jessica Faul and Angelina R Sutin and Osorio Meirelles and Mulas, A and Hofman, A and Andr{\'e} G Uitterlinden and Fernando Rivadeneira and Markus Perola and Wei Zhao and Veikko Salomaa and Kristine Yaffe and Luik, A I and Yongmei Liu and Ding, J and Paul Lichtenstein and Land{\'e}n, M and Elisabeth Widen and David R Weir and David J Llewellyn and Murray, A and Sharon L R Kardia and Johan G Eriksson and Karestan C Koenen and Patrik K E Magnusson and Luigi Ferrucci and Thomas H Mosley and Francesco Cucca and Ben A Oostra and David A Bennett and Paunio, T. and Klaus Berger and Tamara B Harris and Nancy L Pedersen and Joanne M Murabito and Henning Tiemeier and Cornelia M van Duijn and Katri R{\"a}ikk{\"o}nen} } @article {9022, title = {Validating Mortality Ascertainment in the Health and Retirement Study}, year = {2016}, month = {11/2016}, institution = {Survey Research Center, Institute for Social Research, University of Michigan}, address = {Ann Arbor, Michigan}, abstract = {Accurate tracking of mortality is of central importance in longitudinal studies of older populations, both as an important health outcome and as a necessary part of accounting for the representativeness of the panel over time. For nationally representative studies where good population life tables exist the quality of mortality ascertainment can be validated by comparison with life tables. This is demonstrated here for the Health and Retirement Study (HRS), using both period and cohort comparisons from 1992-2011. Mortality ascertainment in the HRS is effectively complete.}, author = {David R Weir} } @article {8314, title = {Childhood and later life stressors and increased inflammatory gene expression at older ages.}, journal = {Soc Sci Med}, volume = {130}, year = {2015}, note = {Times Cited: 0 0}, month = {2015 Apr}, pages = {16-22}, publisher = {130}, abstract = {

Adverse experiences in early life have the ability to "get under the skin" and affect future health. This study examined the relative influence of adversities during childhood and adulthood in accounting for individual differences in pro-inflammatory gene expression in late life. Using a pilot-sample from the Health and Retirement Study (N = 114) aged from 51 to 95, OLS regression models were run to determine the association between a composite score from three proinflammatory gene expression levels (PTGS2, ILIB, and IL8) and 1) childhood trauma, 2) childhood SES, 3) childhood health, 4) adult traumas, and 5) low SES in adulthood. Our results showed that only childhood trauma was found to be associated with increased inflammatory transcription in late life. Furthermore, examination of interaction effects showed that childhood trauma exacerbated the influence of low SES in adulthood on elevated levels of inflammatory gene expression-signifying that having low SES in adulthood was most damaging for persons who had experienced traumatic events during their childhood. Overall our study suggests that traumas experienced during childhood may alter the stress response, leading to more sensitive reactivity throughout the lifespan. As a result, individuals who experienced greater adversity in early life may be at higher risk of late life health outcomes, particularly if adulthood adversity related to SES persists.

}, keywords = {Adolescent, Age Factors, Aged, Aged, 80 and over, Body Mass Index, Continental Population Groups, Cyclooxygenase 2, Female, Health Status, Health Surveys, Humans, Interleukin-1beta, Interleukin-8, Life Change Events, Male, Middle Aged, Obesity, RNA, Sex Factors, Smoking, Socioeconomic factors, Stress, Psychological}, issn = {1873-5347}, doi = {10.1016/j.socscimed.2015.01.030}, author = {Morgan E. Levine and Steven W. Cole and David R Weir and Eileen M. Crimmins} } @article {12129, title = {Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity: a systematic review and meta-analysis with evidence from up to 331 175 individuals.}, journal = {Human Molecular Genetics}, volume = {24}, year = {2015}, pages = {3582-3594}, abstract = {

Polymorphisms rs6232 and rs6234/rs6235 in PCSK1 have been associated with extreme obesity [e.g. body mass index (BMI) >= 40 kg/m(2)], but their contribution to common obesity (BMI >= 30 kg/m(2)) and BMI variation in a multi-ethnic context is unclear. To fill this gap, we collected phenotypic and genetic data in up to 331 175 individuals from diverse ethnic groups. This process involved a systematic review of the literature in PubMed, Web of Science, Embase and the NIH GWAS catalog complemented by data extraction from pre-existing GWAS or custom-arrays in consortia and single studies. We employed recently developed global meta-analytic random-effects methods to calculate summary odds ratios (OR) and 95\% confidence intervals (CIs) or beta estimates and standard errors (SE) for the obesity status and BMI analyses, respectively. Significant associations were found with binary obesity status for rs6232 (OR = 1.15, 95\% CI 1.06-1.24, P = 6.08 {\texttimes} 10(-6)) and rs6234/rs6235 (OR = 1.07, 95\% CI 1.04-1.10, P = 3.00 {\texttimes} 10(-7)). Similarly, significant associations were found with continuous BMI for rs6232 (β = 0.03, 95\% CI 0.00-0.07; P = 0.047) and rs6234/rs6235 (β = 0.02, 95\% CI 0.00-0.03; P = 5.57 {\texttimes} 10(-4)). Ethnicity, age and study ascertainment significantly modulated the association of PCSK1 polymorphisms with obesity. In summary, we demonstrate evidence that common gene variation in PCSK1 contributes to BMI variation and susceptibility to common obesity in the largest known meta-analysis published to date in genetic epidemiology.

}, keywords = {Alleles, Body Mass Index, Genetic Predisposition to Disease, Genetic Variation, Humans, Obesity, Odds Ratio, Polymorphism, Single Nucleotide, Proprotein Convertase 1}, issn = {1460-2083}, doi = {10.1093/hmg/ddv097}, author = {Nead, Kevin T and Li, Aihua and Wehner, Mackenzie R and Neupane, Binod and Gustafsson, Stefan and Adam S Butterworth and Engert, James C and Davis, A Darlene and Hegele, Robert A and Miller, Ruby and den Hoed, Marcel and Khaw, Kay-Tee and Kilpel{\"a}inen, Tuomas O and Wareham, Nick and Edwards, Todd L and Hallmans, G{\"o}ran and Varga, Tibor V and Sharon L R Kardia and Smith, Jennifer A and Zhao, Wei and Jessica Faul and David R Weir and Mi, Jie and Xi, Bo and Quinteros, Samuel Canizales and Cooper, Cyrus and Sayer, Avan Aihie and Jameson, Karen and Gr{\o}ntved, Anders and Myriam Fornage and Stephen Sidney and Hanis, Craig L and Highland, Heather M and H{\"a}ring, Hans-Ulrich and Heni, Martin and Lasky-Su, Jessica and Weiss, Scott T and Gerhard, Glenn S and Still, Christopher and Melka, Melkaey M and Pausova, Zdenka and Paus, Tom{\'a}{\v s} and Grant, Struan F A and Hakonarson, Hakon and Price, R Arlen and Wang, Kai and Scherag, Andre and Hebebrand, Johannes and Hinney, Anke and Franks, Paul W and Timothy M Frayling and McCarthy, Mark I and Hirschhorn, Joel N and Ruth J F Loos and Ingelsson, Erik and Gerstein, Hertzel C and Yusuf, Salim and Beyene, Joseph and Anand, Sonia S and Meyre, David} } @article {8884, title = {Directional dominance on stature and cognition in~diverse human populations.}, journal = {Nature}, volume = {523}, year = {2015}, month = {2015 Jul 23}, pages = {459-62}, abstract = {

Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs~of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 {\texttimes} 10(-300), 2.1 {\texttimes} 10(-6), 2.5 {\texttimes} 10(-10) and 1.8 {\texttimes} 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months{\textquoteright} less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

}, keywords = {Biological Evolution, Blood pressure, Body Height, Cholesterol, Cognitive Ability, Cohort Studies, Education, Female, Forced Expiratory Volume, Genome, Homozygote, Humans, Lung Volume Measurements, Male, Phenotype}, issn = {1476-4687}, doi = {10.1038/nature14618}, author = {Joshi, Peter K and T{\~o}nu Esko and Mattsson, Hannele and Eklund, Niina and Gandin, Ilaria and Nutile, Teresa and Jackson, Anne U and Schurmann, Claudia and Albert Vernon Smith and Zhang, Weihua and Okada, Yukinori and Stan{\v c}{\'a}kov{\'a}, Alena and Jessica Faul and Wei Zhao and Traci M Bartz and Maria Pina Concas and Franceschini, Nora and Enroth, Stefan and Vitart, Veronique and Trompet, Stella and Guo, Xiuqing and Daniel I Chasman and Jeff O{\textquoteright}Connell and Corre, Tanguy and Nongmaithem, Suraj S and Chen, Yuning and Mangino, Massimo and Ruggiero, Daniela and Traglia, Michela and Farmaki, Aliki-Eleni and Kacprowski, Tim and Bjonnes, Andrew and van der Spek, Ashley and Wu, Ying and Giri, Anil K and Yanek, Lisa R and Wang, Lihua and Edith Hofer and Cornelius A Rietveld and McLeod, Olga and Marilyn C Cornelis and Pattaro, Cristian and Verweij, Niek and Baumbach, Clemens and Abdel Abdellaoui and Warren, Helen R and Vuckovic, Dragana and Mei, Hao and Bouchard, Claude and Perry, John R B and Cappellani, Stefania and Saira S Mirza and Benton, Miles C and Broeckel, Ulrich and Sarah E Medland and Penelope A Lind and Malerba, Giovanni and Alexander W Drong and Yengo, Loic and Bielak, Lawrence F and Zhi, Degui and van der Most, Peter J and Daniel Shriner and M{\"a}gi, Reedik and Hemani, Gibran and Karaderi, Tugce and Wang, Zhaoming and Tian Liu and Demuth, Ilja and Jing Hua Zhao and Meng, Weihua and Lataniotis, Lazaros and van der Laan, Sander W and Bradfield, Jonathan P and Andrew R Wood and Bonnefond, Amelie and Ahluwalia, Tarunveer S and Hall, Leanne M and Salvi, Erika and Yazar, Seyhan and Carstensen, Lisbeth and de Haan, Hugoline G and Abney, Mark and Afzal, Uzma and Matthew A. Allison and Amin, Najaf and Asselbergs, Folkert W and Bakker, Stephan J L and Barr, R Graham and Baumeister, Sebastian E and Daniel J. Benjamin and Bergmann, Sven and Boerwinkle, Eric and Erwin P Bottinger and Campbell, Archie and Chakravarti, Aravinda and Chan, Yingleong and Chanock, Stephen J and Chen, Constance and Yii-Der I Chen and Collins, Francis S and Connell, John and Correa, Adolfo and Cupples, L Adrienne and Gail Davies and D{\"o}rr, Marcus and Georg B Ehret and Ellis, Stephen B and Feenstra, Bjarke and Feitosa, Mary F and Ford, Ian and Caroline S Fox and Timothy M Frayling and Friedrich, Nele and Geller, Frank and Scotland, Generation and Gillham-Nasenya, Irina and Gottesman, Omri and Graff, Misa and Grodstein, Francine and Gu, Charles and Haley, Chris and Hammond, Christopher J and Sarah E Harris and Tamara B Harris and Nicholas D Hastie and Heard-Costa, Nancy L and Heikkil{\"a}, Kauko and Lynne J Hocking and Homuth, Georg and Jouke-Jan Hottenga and Huang, Jinyan and Huffman, Jennifer E and Hysi, Pirro G and Mohammed Arfan Ikram and Ingelsson, Erik and Joensuu, Anni and Johansson, {\r A}sa and Jousilahti, Pekka and Jukema, J Wouter and K{\"a}h{\"o}nen, Mika and Kamatani, Yoichiro and Kanoni, Stavroula and Kerr, Shona M and Khan, Nazir M and Philipp D Koellinger and Koistinen, Heikki A and Kooner, Manraj K and Kubo, Michiaki and Kuusisto, Johanna and Lahti, Jari and Lenore J Launer and Lea, Rodney A and Lehne, Benjamin and Lehtim{\"a}ki, Terho and David C Liewald and Lars Lind and Loh, Marie and Lokki, Marja-Liisa and London, Stephanie J and Loomis, Stephanie J and Loukola, Anu and Lu, Yingchang and Lumley, Thomas and Lundqvist, Annamari and M{\"a}nnist{\"o}, Satu and Marques-Vidal, Pedro and Masciullo, Corrado and Matchan, Angela and Mathias, Rasika A and Matsuda, Koichi and Meigs, James B and Meisinger, Christa and Meitinger, Thomas and Menni, Cristina and Mentch, Frank D and Mihailov, Evelin and Lili Milani and Montasser, May E and Grant W Montgomery and Alanna C Morrison and Myers, Richard H and Nadukuru, Rajiv and Navarro, Pau and Nelis, Mari and Nieminen, Markku S and Ilja M Nolte and O{\textquoteright}Connor, George T and Ogunniyi, Adesola and Padmanabhan, Sandosh and Walter R Palmas and Pankow, James S and Patarcic, Inga and Pavani, Francesca and Peyser, Patricia A and Pietilainen, Kirsi and Neil Poulter and Prokopenko, Inga and Ralhan, Sarju and Redmond, Paul and Rich, Stephen S and Rissanen, Harri and Robino, Antonietta and Rose, Lynda M and Rose, Richard and Cinzia Felicita Sala and Babatunde Salako and Veikko Salomaa and Sarin, Antti-Pekka and Saxena, Richa and Schmidt, Helena and Scott, Laura J and Scott, William R and Sennblad, Bengt and Seshadri, Sudha and Peter Sever and Shrestha, Smeeta and Smith, Blair H and Jennifer A Smith and Soranzo, Nicole and Sotoodehnia, Nona and Southam, Lorraine and Stanton, Alice V and Stathopoulou, Maria G and Strauch, Konstantin and Strawbridge, Rona J and Suderman, Matthew J and Tandon, Nikhil and Tang, Sian-Tsun and Kent D Taylor and Bamidele O Tayo and T{\"o}glhofer, Anna Maria and Tomaszewski, Maciej and T{\v s}ernikova, Natalia and Tuomilehto, Jaakko and Andr{\'e} G Uitterlinden and Vaidya, Dhananjay and van Hylckama Vlieg, Astrid and van Setten, Jessica and Vasankari, Tuula and Vedantam, Sailaja and Vlachopoulou, Efthymia and Vozzi, Diego and Vuoksimaa, Eero and Waldenberger, Melanie and Erin B Ware and Wentworth-Shields, William and Whitfield, John B and Sarah Wild and Gonneke Willemsen and Yajnik, Chittaranjan S and Yao, Jie and Zaza, Gianluigi and Zhu, Xiaofeng and Salem, Rany M and Melbye, Mads and Bisgaard, Hans and Nilesh J Samani and Cusi, Daniele and Mackey, David A and Cooper, Richard S and Froguel, Philippe and Pasterkamp, Gerard and Grant, Struan F A and Hakonarson, Hakon and Luigi Ferrucci and Scott, Robert A and Morris, Andrew D and Palmer, Colin N A and George Dedoussis and Deloukas, Panos and Bertram, Lars and Lindenberger, Ulman and Berndt, Sonja I and Lindgren, Cecilia M and Nicholas J Timpson and T{\"o}njes, Anke and Munroe, Patricia B and Thorkild I. A. S{\o}rensen and Charles N Rotimi and Donna K Arnett and Oldehinkel, Albertine J and Sharon L R Kardia and Balkau, Beverley and Gambaro, Giovanni and Morris, Andrew P and Johan G Eriksson and Margaret J Wright and Nicholas G Martin and Hunt, Steven C and John M Starr and Ian J Deary and Griffiths, Lyn R and Henning Tiemeier and Nicola Pirastu and Kaprio, Jaakko and Wareham, Nicholas J and P{\'e}russe, Louis and Wilson, James G and Giorgia G Girotto and Caulfield, Mark J and Olli T Raitakari and Dorret I Boomsma and Gieger, Christian and van der Harst, Pim and Hicks, Andrew A and Kraft, Peter and Sinisalo, Juha and Knekt, Paul and Johannesson, Magnus and Patrik K E Magnusson and Hamsten, Anders and Schmidt, Reinhold and Ingrid B Borecki and Vartiainen, Erkki and Becker, Diane M and Bharadwaj, Dwaipayan and Mohlke, Karen L and Boehnke, Michael and Cornelia M van Duijn and Sanghera, Dharambir K and Teumer, Alexander and Zeggini, Eleftheria and Andres Metspalu and Paolo P. Gasparini and Ulivi, Sheila and Ober, Carole and Toniolo, Daniela and Rudan, Igor and David J Porteous and Ciullo, Marina and Timothy Spector and Caroline Hayward and Dupuis, Jos{\'e}e and Ruth J F Loos and Alan F Wright and Chandak, Giriraj R and Vollenweider, Peter and Alan R Shuldiner and Ridker, Paul M and Rotter, Jerome I and Sattar, Naveed and Gyllensten, Ulf and Kari E North and Pirastu, Mario and Psaty, Bruce M and David R Weir and Laakso, Markku and Gudnason, Vilmundur and Takahashi, Atsushi and Chambers, John C and Kooner, Jaspal S and David P Strachan and Campbell, Harry and Joel N Hirschhron and Markus Perola and Polasek, Ozren and James F Wilson} } @article {8519, title = {Documentation of Biomarkers in the 2010 and 2012 Health and Retirement Study}, number = {DR-031}, year = {2015}, month = {04/2015}, pages = {15}, institution = {Survey Research Center, University of Michigan}, address = {Ann Arbor, Michigan}, keywords = {Biomarkers, Meta-analyses, Survey Methodology}, author = {Eileen M. Crimmins and Jessica Faul and Jung K Kim and David R Weir} } @article {8882, title = {Genetic studies of body mass index yield new insights for obesity biology.}, journal = {Nature}, volume = {518}, year = {2015}, month = {2015 Feb 12}, pages = {197-206}, abstract = {

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P~<~5~{\texttimes}~10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for \~{}2.7\% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20\% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

}, keywords = {Age Factors, BMI, Continental Population Groups, Energy Metabolism, Europe, Female, Genome-Wide Association Study, Glutamic Acid, Humans, Insulin, Male, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Synapses}, issn = {1476-4687}, doi = {10.1038/nature14177}, author = {Locke, Adam E and Kahali, Bratati and Berndt, Sonja I and Justice, Anne E and Pers, Tune H and Day, Felix R and Powell, Corey and Vedantam, Sailaja and Buchkovich, Martin L and Yang, Jian and Croteau-Chonka, Damien C and T{\~o}nu Esko and Fall, Tove and Ferreira, Teresa and Gustafsson, Stefan and Kutalik, Zolt{\'a}n and Luan, Jian{\textquoteright}an and M{\"a}gi, Reedik and Randall, Joshua C and Thomas W Winkler and Andrew R Wood and Workalemahu, Tsegaselassie and Jessica Faul and Jennifer A Smith and Jing Hua Zhao and Wei Zhao and Chen, Jin and Rudolf Ferhmann and Hedman, {\r A}sa K and Karjalainen, Juha and Schmidt, Ellen M and Absher, Devin and Amin, Najaf and Anderson, Denise and Beekman, Marian and Bolton, Jennifer L and Bragg-Gresham, Jennifer L and Buyske, Steven and Demirkan, Ayse and Deng, Guohong and Georg B Ehret and Feenstra, Bjarke and Feitosa, Mary F and Fischer, Krista and Goel, Anuj and Gong, Jian and Jackson, Anne U and Kanoni, Stavroula and Kleber, Marcus E and Kristiansson, Kati and Lim, Unhee and Lotay, Vaneet and Mangino, Massimo and Irene Mateo Leach and Medina-Gomez, Carolina and Sarah E Medland and Michael A Nalls and Palmer, Cameron D and Pasko, Dorota and Pechlivanis, Sonali and Peters, Marjolein J and Prokopenko, Inga and Shungin, Dmitry and Stan{\v c}{\'a}kov{\'a}, Alena and Strawbridge, Rona J and Yun Ju Sung and Toshiko Tanaka and Teumer, Alexander and Trompet, Stella and van der Laan, Sander W and van Setten, Jessica and Jana V. van Vliet-Ostaptchouk and Wang, Zhaoming and Yengo, Loic and Zhang, Weihua and Isaacs, Aaron and Albrecht, Eva and {\"A}rnl{\"o}v, Johan and Arscott, Gillian M and Attwood, Antony P and Bandinelli, Stefania and Barrett, Amy and Bas, Isabelita N and Bellis, Claire and Bennett, Amanda J and Berne, Christian and Blagieva, Roza and Bl{\"u}her, Matthias and B{\"o}hringer, Stefan and Bonnycastle, Lori L and B{\"o}ttcher, Yvonne and Boyd, Heather A and Bruinenberg, Marcel and Caspersen, Ida H and Yii-Der I Chen and Robert Clark and Daw, E Warwick and de Craen, Anton J M and Delgado, Graciela and Dimitriou, Maria and Doney, Alex S F and Eklund, Niina and Estrada, Karol and Eury, Elodie and Folkersen, Lasse and Fraser, Ross M and Melissa E Garcia and Geller, Frank and Giedraitis, Vilmantas and Gigante, Bruna and Alan S Go and Golay, Alain and Goodall, Alison H and Gordon, Scott D and Gorski, Mathias and Hans-J{\"o}rgen Grabe and Grallert, Harald and Grammer, Tanja B and Gr{\"a}{\ss}ler, J{\"u}rgen and Gr{\"o}nberg, Henrik and Groves, Christopher J and Gusto, Ga{\"e}lle and Jeffrey Haessler and Hall, Per and Haller, Toomas and Hallmans, G{\"o}ran and Catharina A Hartman and Hassinen, Maija and Caroline Hayward and Heard-Costa, Nancy L and Helmer, Quinta and Hengstenberg, Christian and Oddgeir L Holmen and Jouke-Jan Hottenga and James, Alan L and Janina Jeff and Johansson, {\r A}sa and Jolley, Jennifer and Juliusdottir, Thorhildur and Kinnunen, Leena and Koenig, Wolfgang and Koskenvuo, Markku and Kratzer, Wolfgang and Laitinen, Jaana and Lamina, Claudia and Leander, Karin and Lee, Nanette R and Lichtner, Peter and Lars Lind and Lindstr{\"o}m, Jaana and Ken Sin Lo and Lobbens, St{\'e}phane and Lorbeer, Roberto and Lu, Yingchang and Mach, Fran{\c c}ois and Patrik K E Magnusson and Mahajan, Anubha and McArdle, Wendy L and McLachlan, Stela and Menni, Cristina and Merger, Sigrun and Mihailov, Evelin and Lili Milani and Moayyeri, Alireza and Monda, Keri L and Morken, Mario A and Mulas, Antonella and M{\"u}ller, Gabriele and M{\"u}ller-Nurasyid, Martina and Musk, Arthur W and Nagaraja, Ramaiah and Markus M N{\"o}then and Ilja M Nolte and Pilz, Stefan and Nigel W Rayner and Renstrom, Frida and Rettig, Rainer and Ried, Janina S and Ripke, Stephan and Neil R Robertson and Rose, Lynda M and Sanna, Serena and Scharnagl, Hubert and Scholtens, Salome and Schumacher, Fredrick R and Scott, William R and Seufferlein, Thomas and Jianxin Shi and Albert Vernon Smith and Smolonska, Joanna and Stanton, Alice V and Steinthorsdottir, Valgerdur and Kathleen E Stirrups and Heather M Stringham and Sundstr{\"o}m, Johan and Swertz, Morris A and Swift, Amy J and Syv{\"a}nen, Ann-Christine and Tan, Sian-Tsung and Bamidele O Tayo and Thorand, Barbara and Thorleifsson, Gudmar and Tyrer, Jonathan P and Uh, Hae-Won and Vandenput, Liesbeth and Verhulst, Frank C and Vermeulen, Sita H and Verweij, Niek and Vonk, Judith M and Lindsay L Waite and Warren, Helen R and Dawn M Waterworth and Michael N Weedon and Wilkens, Lynne R and Willenborg, Christina and Wilsgaard, Tom and Wojczynski, Mary K and Wong, Andrew and Alan F Wright and Zhang, Qunyuan and Brennan, Eoin P and Murim Choi and Dastani, Zari and Alexander W Drong and Eriksson, Per and Franco-Cereceda, Anders and G{\r a}din, Jesper R and Gharavi, Ali G and Goddard, Michael E and Handsaker, Robert E and Huang, Jinyan and Karpe, Fredrik and Kathiresan, Sekar and Keildson, Sarah and Kiryluk, Krzysztof and Kubo, Michiaki and Lee, Jong-Young and Liang, Liming and Lifton, Richard P and Ma, Baoshan and McCarroll, Steven A and McKnight, Amy J and Min, Josine L and Moffatt, Miriam F and Grant W Montgomery and Joanne M Murabito and Nicholson, George and Nyholt, Dale R and Okada, Yukinori and Perry, John R B and Dorajoo, Rajkumar and Reinmaa, Eva and Salem, Rany M and Sandholm, Niina and Scott, Robert A and Stolk, Lisette and Takahashi, Atsushi and Tanaka, Toshihiro and Ferdinand M van {\textquoteright}t Hooft and Anna A E Vinkhuyzen and Westra, Harm-Jan and Wei Zhang and Krina T Zondervan and Andrew C Heath and Arveiler, Dominique and Bakker, Stephan J L and Beilby, John and Bergman, Richard N and Blangero, John and Bovet, Pascal and Campbell, Harry and Caulfield, Mark J and Cesana, Giancarlo and Chakravarti, Aravinda and Daniel I Chasman and Chines, Peter S and Collins, Francis S and Crawford, Dana C and Cupples, L Adrienne and Cusi, Daniele and Danesh, John and de Faire, Ulf and Hester M den Ruijter and Dominiczak, Anna F and Erbel, Raimund and Erdmann, Jeanette and Johan G Eriksson and Farrall, Martin and Felix, Stephan B and Ferrannini, Ele and Ferri{\`e}res, Jean and Ford, Ian and Forouhi, Nita G and Forrester, Terrence and Franco, Oscar H and Gansevoort, Ron T and Gejman, Pablo V and Gieger, Christian and Gottesman, Omri and Gudnason, Vilmundur and Gyllensten, Ulf and Hall, Alistair S and Tamara B Harris and Andrew T Hattersley and Hicks, Andrew A and Hindorff, Lucia A and Aroon Hingorani and Hofman, Albert and Homuth, Georg and Hovingh, G Kees and Humphries, Steve E and Hunt, Steven C and Hypp{\"o}nen, Elina and Illig, Thomas and Jacobs, Kevin B and J{\"a}rvelin, Marjo-Riitta and J{\"o}ckel, Karl-Heinz and Johansen, Berit and Jousilahti, Pekka and Jukema, J Wouter and Jula, Antti M and Kaprio, Jaakko and Kastelein, John J P and Keinanen-Kiukaanniemi, Sirkka M and Lambertus A Kiemeney and Knekt, Paul and Kooner, Jaspal S and Charles Kooperberg and Kovacs, Peter and Kraja, Aldi T and Kumari, Meena and Kuusisto, Johanna and Lakka, Timo A and Langenberg, Claudia and Loic Le Marchand and Lehtim{\"a}ki, Terho and Lyssenko, Valeriya and M{\"a}nnist{\"o}, Satu and Marette, Andr{\'e} and Matise, Tara C and McKenzie, Colin A and McKnight, Barbara and Moll, Frans L and Morris, Andrew D and Morris, Andrew P and Murray, Jeffrey C and Nelis, Mari and Ohlsson, Claes and Oldehinkel, Albertine J and Ong, Ken K and Pamela A F Madden and Pasterkamp, Gerard and Peden, John F and Peters, Annette and Postma, Dirkje S and Pramstaller, Peter P and Price, Jackie F and Qi, Lu and Olli T Raitakari and Rankinen, Tuomo and Rao, D C and Rice, Treva K and Ridker, Paul M and Rioux, John D and Ritchie, Marylyn D and Rudan, Igor and Veikko Salomaa and Nilesh J Samani and Saramies, Jouko and Sarzynski, Mark A and Schunkert, Heribert and Schwarz, Peter E H and Peter Sever and Alan R Shuldiner and Sinisalo, Juha and Stolk, Ronald P and Strauch, Konstantin and T{\"o}njes, Anke and Tr{\'e}gou{\"e}t, David-Alexandre and Tremblay, Angelo and Tremoli, Elena and Virtamo, Jarmo and Vohl, Marie-Claude and V{\"o}lker, Uwe and Waeber, G{\'e}rard and Gonneke Willemsen and Witteman, Jacqueline C and Zillikens, M Carola and Adair, Linda S and Amouyel, Philippe and Asselbergs, Folkert W and Assimes, Themistocles L and Bochud, Murielle and Boehm, Bernhard O and Boerwinkle, Eric and Bornstein, Stefan R and Erwin P Bottinger and Bouchard, Claude and Cauchi, St{\'e}phane and Chambers, John C and Chanock, Stephen J and Cooper, Richard S and de Bakker, Paul I W and George Dedoussis and Luigi Ferrucci and Franks, Paul W and Froguel, Philippe and Leif C Groop and Christopher A Haiman and Hamsten, Anders and Hui, Jennie and Hunter, David J and Hveem, Kristian and Kaplan, Robert C and Mika Kivim{\"a}ki and Kuh, Diana and Laakso, Markku and Yongmei Liu and Nicholas G Martin and M{\"a}rz, Winfried and Melbye, Mads and Andres Metspalu and Moebus, Susanne and Munroe, Patricia B and Nj{\o}lstad, Inger and Ben A Oostra and Palmer, Colin N A and Nancy L Pedersen and Markus Perola and P{\'e}russe, Louis and Peters, Ulrike and Power, Chris and Quertermous, Thomas and Rauramaa, Rainer and Fernando Rivadeneira and Saaristo, Timo E and Saleheen, Danish and Sattar, Naveed and Eric E Schadt and Schlessinger, David and Eline P Slagboom and Snieder, Harold and Timothy Spector and Thorsteinsdottir, Unnur and Stumvoll, Michael and Tuomilehto, Jaakko and Andr{\'e} G Uitterlinden and Uusitupa, Matti and van der Harst, Pim and Walker, Mark and Wallaschofski, Henri and Wareham, Nicholas J and Watkins, Hugh and David R Weir and Wichmann, H-Erich and James F Wilson and Zanen, Pieter and Ingrid B Borecki and Deloukas, Panos and Caroline S Fox and Iris M Heid and Jeff O{\textquoteright}Connell and David P Strachan and Stefansson, Kari and Cornelia M van Duijn and Gon{\c c}alo R Abecasis and Lude L Franke and Timothy M Frayling and McCarthy, Mark I and Peter M Visscher and Scherag, Andre and Willer, Cristen J and Boehnke, Michael and Mohlke, Karen L and Lindgren, Cecilia M and Beckmann, Jacques S and Barroso, In{\^e}s and Kari E North and Ingelsson, Erik and Joel N Hirschhron and Ruth J F Loos and Elizabeth K Speliotes} } @article {8606, title = {GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {70}, year = {2015}, month = {2015 Jan}, pages = {110-8}, abstract = {

BACKGROUND: The genetic contribution to longevity in humans has been estimated to range from 15\% to 25\%. Only two genes, APOE and FOXO3, have shown association with longevity in multiple independent studies.

METHODS: We conducted a meta-analysis of genome-wide association studies including 6,036 longevity cases, age >=90 years, and 3,757 controls that died between ages 55 and 80 years. We additionally attempted to replicate earlier identified single nucleotide polymorphism (SNP) associations with longevity.

RESULTS: In our meta-analysis, we found suggestive evidence for the association of SNPs near CADM2 (odds ratio [OR] = 0.81; p value = 9.66 {\texttimes} 10(-7)) and GRIK2 (odds ratio = 1.24; p value = 5.09 {\texttimes} 10(-8)) with longevity. When attempting to replicate findings earlier identified in genome-wide association studies, only the APOE locus consistently replicated. In an additional look-up of the candidate gene FOXO3, we found that an earlier identified variant shows a highly significant association with longevity when including published data with our meta-analysis (odds ratio = 1.17; p value = 1.85{\texttimes}10(-10)).

CONCLUSIONS: We did not identify new genome-wide significant associations with longevity and did not replicate earlier findings except for APOE and FOXO3. Our inability to find new associations with survival to ages >=90 years because longevity represents multiple complex traits with heterogeneous genetic underpinnings, or alternatively, that longevity may be regulated by rare variants that are not captured by standard genome-wide genotyping and imputation of common variants.

}, keywords = {Aged, Aged, 80 and over, Apolipoproteins E, Cell Adhesion Molecules, Cohort Studies, Female, Forkhead Box Protein O3, Forkhead Transcription Factors, Genome-Wide Association Study, Humans, Longevity, Male, Middle Aged, Polymorphism, Single Nucleotide, Receptors, Kainic Acid}, issn = {1758-535X}, doi = {10.1093/gerona/glu166}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296168/}, author = {Broer, Linda and Aron S Buchman and Deelen, Joris and Daniel S Evans and Jessica Faul and Kathryn L Lunetta and Sebastiani, Paola and Jennifer A Smith and Albert Vernon Smith and Toshiko Tanaka and Lei Yu and Alice M. Arnold and Aspelund, Thor and Emelia J Benjamin and Philip L de Jager and Gu{\dh}ny Eir{\'\i}ksd{\'o}ttir and Melissa E Garcia and Hofman, Albert and Kaplan, Robert C and Sharon L R Kardia and Douglas P Kiel and Ben A Oostra and Orwoll, Eric S and Parimi, Neeta and Psaty, Bruce M and Fernando Rivadeneira and Rotter, Jerome I and Seshadri, Sudha and Andrew B Singleton and Henning Tiemeier and Andr{\'e} G Uitterlinden and Wei Zhao and Bandinelli, Stefania and David A Bennett and Luigi Ferrucci and Gudnason, Vilmundur and Tamara B Harris and Karasik, David and Lenore J Launer and Thomas T Perls and Eline P Slagboom and Tranah, Gregory J and David R Weir and Anne B Newman and Cornelia M van Duijn and Joanne M Murabito} } @article {8889, title = {Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.}, journal = {Nat Genet}, volume = {47}, year = {2015}, month = {2015 Nov}, pages = {1294-303}, abstract = {

Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in \~{}70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (\~{}6\% increase in risk per year; P = 3 {\texttimes} 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.

}, keywords = {Age Factors, Aging, BRCA1 Protein, Breast Neoplasms, DNA Repair, Female, Genome, Genome-Wide Association Study, Genotype, Humans, Hypothalamus, Menopause, Middle Aged, Models, Genetic, Older Adults, Phenotype, Reproduction, Signal Transduction}, issn = {1546-1718}, doi = {10.1038/ng.3412}, author = {Day, Felix R and Ruth, Katherine S and Thompson, Deborah J and Kathryn L Lunetta and Pervjakova, Natalia and Daniel I Chasman and Stolk, Lisette and Finucane, Hilary K and Sulem, Patrick and Bulik-Sullivan, Brendan and T{\~o}nu Esko and Andrew D Johnson and Elks, Cathy E and Franceschini, Nora and He, Chunyan and Altmaier, Elisabeth and Brody, Jennifer A and Lude L Franke and Huffman, Jennifer E and Keller, Margaux F and McArdle, Patrick F and Nutile, Teresa and Porcu, Eleonora and Robino, Antonietta and Rose, Lynda M and Schick, Ursula M and Jennifer A Smith and Teumer, Alexander and Traglia, Michela and Vuckovic, Dragana and Yao, Jie and Wei Zhao and Albrecht, Eva and Amin, Najaf and Corre, Tanguy and Jouke-Jan Hottenga and Mangino, Massimo and Albert Vernon Smith and Toshiko Tanaka and Gon{\c c}alo R Abecasis and Andrulis, Irene L and Anton-Culver, Hoda and Antoniou, Antonis C and Arndt, Volker and Alice M. Arnold and Barbieri, Caterina and Beckmann, Matthias W and Beeghly-Fadiel, Alicia and Benitez, Javier and Bernstein, Leslie and Bielinski, Suzette J and Blomqvist, Carl and Boerwinkle, Eric and Bogdanova, Natalia V and Bojesen, Stig E and Manjeet K. Bolla and Borresen-Dale, Anne-Lise and Boutin, Thibaud S and Brauch, Hiltrud and Brenner, Hermann and Br{\"u}ning, Thomas and Burwinkel, Barbara and Campbell, Archie and Campbell, Harry and Chanock, Stephen J and Chapman, J Ross and Yii-Der I Chen and Chenevix-Trench, Georgia and Couch, Fergus J and Coviello, Andrea D and Cox, Angela and Czene, Kamila and Darabi, Hatef and De Vivo, Immaculata and Ellen W Demerath and Joe G Dennis and Devilee, Peter and D{\"o}rk, Thilo and Dos-Santos-Silva, Isabel and Dunning, Alison M and John D Eicher and Fasching, Peter A and Jessica Faul and Figueroa, Jonine and Flesch-Janys, Dieter and Gandin, Ilaria and Melissa E Garcia and Garc{\'\i}a-Closas, Montserrat and Giles, Graham G and Giorgia G Girotto and Goldberg, Mark S and Gonz{\'a}lez-Neira, Anna and Goodarzi, Mark O and Grove, Megan L and Gudbjartsson, Daniel F and Gu{\'e}nel, Pascal and Guo, Xiuqing and Christopher A Haiman and Hall, Per and Hamann, Ute and Henderson, Brian E and Lynne J Hocking and Hofman, Albert and Homuth, Georg and Hooning, Maartje J and John L Hopper and Hu, Frank B and Huang, Jinyan and Humphreys, Keith and Hunter, David J and Jakubowska, Anna and Jones, Samuel E and Kabisch, Maria and Karasik, David and Knight, Julia A and Kolcic, Ivana and Charles Kooperberg and Kosma, Veli-Matti and Kriebel, Jennifer and Kristensen, Vessela and Lambrechts, Diether and Langenberg, Claudia and Li, Jingmei and Li, Xin and Lindstr{\"o}m, Sara and Yongmei Liu and Luan, Jian{\textquoteright}an and Lubinski, Jan and M{\"a}gi, Reedik and Mannermaa, Arto and Manz, Judith and Margolin, Sara and Marten, Jonathan and Nicholas G Martin and Masciullo, Corrado and Meindl, Alfons and Michailidou, Kyriaki and Mihailov, Evelin and Lili Milani and Milne, Roger L and M{\"u}ller-Nurasyid, Martina and Michael A Nalls and Neale, Benjamin M and Nevanlinna, Heli and Neven, Patrick and Anne B Newman and B{\o}rge G Nordestgaard and Olson, Janet E and Padmanabhan, Sandosh and Peterlongo, Paolo and Peters, Ulrike and Petersmann, Astrid and Peto, Julian and Pharoah, Paul D P and Nicola Pirastu and Pirie, Ailith and Pistis, Giorgio and Polasek, Ozren and David J Porteous and Psaty, Bruce M and Pylk{\"a}s, Katri and Radice, Paolo and Raffel, Leslie J and Fernando Rivadeneira and Rudan, Igor and Rudolph, Anja and Ruggiero, Daniela and Cinzia Felicita Sala and Sanna, Serena and Sawyer, Elinor J and Schlessinger, David and Schmidt, Marjanka K and Schmidt, Frank and Schmutzler, Rita K and Schoemaker, Minouk J and Scott, Robert A and Seynaeve, Caroline M and Simard, Jacques and Sorice, Rossella and Southey, Melissa C and St{\"o}ckl, Doris and Strauch, Konstantin and Swerdlow, Anthony and Kent D Taylor and Thorsteinsdottir, Unnur and Toland, Amanda E and Tomlinson, Ian and Truong, Th{\'e}r{\`e}se and Tryggvadottir, Laufey and Stephen T Turner and Vozzi, Diego and Wang, Qin and Wellons, Melissa and Gonneke Willemsen and James F Wilson and Winqvist, Robert and Wolffenbuttel, Bruce B H R and Alan F Wright and Yannoukakos, Drakoulis and Zemunik, Tatijana and Wei Zhang and Zygmunt, Marek and Bergmann, Sven and Dorret I Boomsma and Buring, Julie E and Luigi Ferrucci and Grant W Montgomery and Gudnason, Vilmundur and Timothy Spector and Cornelia M van Duijn and Alizadeh, Behrooz Z and Ciullo, Marina and Crisponi, Laura and Easton, Douglas F and Paolo P. Gasparini and Gieger, Christian and Tamara B Harris and Caroline Hayward and Sharon L R Kardia and Kraft, Peter and McKnight, Barbara and Andres Metspalu and Alanna C Morrison and Reiner, Alex P and Ridker, Paul M and Rotter, Jerome I and Toniolo, Daniela and Andr{\'e} G Uitterlinden and Ulivi, Sheila and V{\"o}lzke, Henry and Wareham, Nicholas J and David R Weir and Laura M Yerges-Armstrong and Price, Alkes L and Stefansson, Kari and Visser, Jenny A and Ong, Ken K and Chang-Claude, Jenny and Joanne M Murabito and Perry, John R B and Murray, Anna} } @article {8214, title = {Loneliness, eudaimonia, and the human conserved transcriptional response to adversity.}, journal = {Psychoneuroendocrinology}, volume = {62}, year = {2015}, month = {2015 Dec}, pages = {11-7}, publisher = {62}, abstract = {

BACKGROUND: Chronic social adversity activates a conserved transcriptional response to adversity (CTRA) marked by increased expression of pro-inflammatory genes and decreased expression of antiviral- and antibody-related genes. Recent findings suggest that some psychological resilience factors may help buffer CTRA activation, but the relative impact of resilience and adversity factors remains poorly understood. Here we examined the relative strength of CTRA association for the two best-established psychological correlates of CTRA gene expression-the risk factor of perceived social isolation (loneliness) and the resilience factor of eudaimonic well-being (purpose and meaning in life).

METHODS: Peripheral blood samples and validated measures of loneliness and eudaimonic well-being were analyzed in 108 community-dwelling older adults participating in the longitudinal US Health and Retirement Study (56\% female, mean age 73). Mixed effect linear model analyses quantified the strength of association between CTRA gene expression and measures of loneliness and eudaimonic well-being in separate and joint analyses.

RESULTS: As in previous studies, separate analyses found CTRA gene expression to be up-regulated in association with loneliness and down-regulated in association with eudaimonic well-being. In joint analyses, effects of loneliness were completely abrogated whereas eudaimonic well-being continued to associate with CTRA down-regulation. Similar eudaimonia-dominant effects were observed for positive and negative affect, optimism and pessimism, and anxiety symptoms. All results were independent of demographic and behavioral health risk factors.

CONCLUSIONS: Eudaimonic well-being may have the potential to compensate for the adverse impact of loneliness on CTRA gene expression. Findings suggest a novel approach to targeting the health risks associated with social isolation by promoting purpose and meaning in life.

}, keywords = {Aged, Aged, 80 and over, Down-Regulation, Female, Humans, Inflammation, Loneliness, Longitudinal Studies, Male, Mental Health, Middle Aged, social isolation, Social Support, Stress, Psychological, Transcriptome}, issn = {1873-3360}, doi = {10.1016/j.psyneuen.2015.07.001}, url = {http://www.sciencedirect.com/science/article/pii/S0306453015002358}, author = {Steven W. Cole and Morgan E. Levine and Jesusa M. G. Arevalo and Ma, Jeffrey and David R Weir and Eileen M. Crimmins} } @article {5851, title = {Racial Difference in the Use of VA Health Services}, year = {2015}, institution = {Ann Arbor, MI, Michigan Reirement Research Center, University of Michigan}, abstract = {We study the factors that affect the utilization of health care services administered by the Department of Veterans Affairs (VA) and its racial differences. Due to data limitation, previous research in this regard mostly only focuses on veterans who are VA users or at least eligible for VA services. We fill in the gap in literature with a random sample of veterans 51 and older from the Health and Retirement Study. We find that, among all veterans, those who are black and less healthy are more likely to use VA health services. These factors, nevertheless, are no longer statistically significant after the sample is restricted to veterans who are eligible for VA services. We also find that VA health services and services provided through other channels are at least partial substitutes: VA usage drops when a veteran becomes age eligible for Medicare or when a veteran has health insurance coverage through employment. This drop in usage holds not only among all veterans, but also among veterans eligible for VA services. Finally, perception about the quality of services delivered in VA versus non-VA facilities strongly predicts VA services usage. Those who have favorable views toward VA use VA services more, and the results from variance decomposition suggests a majority part of the racial difference in VA usage can be attributed to the racial difference in such perception.}, url = {http://www.mrrc.isr.umich.edu/publications/papers/pdf/wp334.pdf}, author = {Fang, Chichun and Kenneth M. Langa and Helen G Levy and David R Weir} } @article {8928, title = {Advance directives and nursing home stays associated with less aggressive end-of-life care for patients with severe dementia.}, journal = {Health Affairs}, volume = {33}, year = {2014}, month = {2014 Apr}, pages = {667-74}, abstract = {

The number of older adults with cognitive impairment is increasing, and such adults often require a surrogate to make decisions about health care. However, little is known about the aggressiveness of end-of-life care for these people, especially those who reside in the community. We found that cognitive impairment is common among older adults approaching the end of life, whether they live in the community or in a nursing home, and that nearly 30 percent of patients with severe dementia remained in the community until death. Among those patients, having an advance directive in the form of a living will was associated with significantly less aggressive care at the end of life, compared to similar patients without an advance directive-as measured by Medicare spending ($11,461 less per patient), likelihood of in-hospital death (17.9 percentage points lower), and use of the intensive care unit (9.4 percentage points lower). In contrast, advance directives were not associated with differences in care for people with normal cognition or mild dementia, whether they resided in the community or in a nursing home. Timely advance care planning after a diagnosis of cognitive impairment may be particularly important for older adults who reside in the community.

}, keywords = {Advance directives, Dementia, Disabilities, End-of-life care, Nursing homes, Older Adults}, issn = {1544-5208}, doi = {10.1377/hlthaff.2013.1258}, author = {Lauren Hersch Nicholas and Julie P W Bynum and Theodore J Iwashyna and David R Weir and Kenneth M. Langa} } @article {8517, title = {Cognitive Test Selection for the Harmonized Cognitive Assessment Protocol (HCAP)}, year = {2014}, month = {10/2014}, institution = {Institute for Social Research, University of Michigan}, address = {Ann Arbor, Michigan}, abstract = {The goal of this effort, set by the National Institute on Aging (NIA), is to devise a cognitive assessment that meets the following criteria: 1) Can be administered in the home by a survey interviewer in about one hour, 2) Has sufficient overlap with the 2002/03 HRS-ADAMS study that it can be used to establish trends in prevalence of dementia and cognitive impairment without dementia, and 3) Can be administered comparably and lead to comparably valid diagnoses in other developed and developing countries where HRS-type surveys are conducted. This goal is achievable because of substantial investment by the NIA in data collection in population studies focused on dementia. There is thus now an empirical basis for making test selection. Informant reports are a key element of most population-based approaches to assessment to establish the presence or absence of change in cognitive ability and of limitation in activity resulting from change. We intend to include informant reports in our data collection protocol and in the diagnostic algorithm. This document is focused on cognitive testing of the subject.}, keywords = {Cognitive Ability, HCAP, Meta-analyses, Survey Methodology}, author = {David R Weir and Ryan J McCammon and Lindsay H Ryan and Kenneth M. Langa} } @article {8046, title = {Cohort Profile: the Health and Retirement Study (HRS).}, journal = {Int J Epidemiol}, volume = {43}, year = {2014}, month = {2014 Apr}, pages = {576-85}, publisher = {43}, abstract = {

The Health and Retirement Study (HRS) is a nationally representative longitudinal survey of more than 37 000 individuals over age 50 in 23 000 households in the USA. The survey, which has been fielded every 2 years since 1992, was established to provide a national resource for data on the changing health and economic circumstances associated with ageing at both individual and population levels. Its multidisciplinary approach is focused on four broad topics-income and wealth; health, cognition and use of healthcare services; work and retirement; and family connections. HRS data are also linked at the individual level to administrative records from Social Security and Medicare, Veteran{\textquoteright}s Administration, the National Death Index and employer-provided pension plan information. Since 2006, data collection has expanded to include biomarkers and genetics as well as much greater depth in psychology and social context. This blend of economic, health and psychosocial information provides unprecedented potential to study increasingly complex questions about ageing and retirement. The HRS has been a leading force for rapid release of data while simultaneously protecting the confidentiality of respondents. Three categories of data-public, sensitive and restricted-can be accessed through procedures described on the HRS website (hrsonline.isr.umich.edu).

}, keywords = {Aged, Female, Genetic Predisposition to Disease, Health Status, Humans, Longitudinal Studies, Male, Mental Health, Middle Aged, Physical Fitness, Retirement, United States}, issn = {1464-3685}, doi = {10.1093/ije/dyu067}, author = {Amanda Sonnega and Jessica Faul and Mary Beth Ofstedal and Kenneth M. Langa and John W R Phillips and David R Weir} } @article {7996, title = {Development and validation of a brief dementia screening indicator for primary care.}, journal = {Alzheimers Dement}, volume = {10}, year = {2014}, note = {Export Date: 21 April 2014 Source: Scopus Article in Press}, month = {2014 Nov}, pages = {656-665.e1}, publisher = {10}, abstract = {

BACKGROUND: Detection of "any cognitive impairment" is mandated as part of the Medicare annual wellness visit, but screening all patients may result in excessive false positives.

METHODS: We developed and validated a brief Dementia Screening Indicator using data from four large, ongoing cohort studies (the Cardiovascular Health Study [CHS]; the Framingham Heart Study [FHS]; the Health and Retirement Study [HRS]; the Sacramento Area Latino Study on Aging [SALSA]) to help clinicians identify a subgroup of high-risk patients to target for cognitive screening.

RESULTS: The final Dementia Screening Indicator included age (1 point/year; ages, 65-79 years), less than 12~years of education (9 points), stroke (6 points), diabetes mellitus (3 points), body mass index less than 18.5~kg/m(2) (8 points), requiring assistance with money or medications (10 points), and~depressive symptoms (6 points). Accuracy was good across the cohorts (Harrell{\textquoteright}s C statistic: CHS, 0.68; FHS, 0.77; HRS, 0.76; SALSA, 0.78).

CONCLUSIONS: The Dementia Screening Indicator is a simple tool that may be useful in primary care settings to identify high-risk patients to target for cognitive screening.

}, keywords = {Aged, Cohort Studies, Dementia, Female, Humans, Male, Mass Screening, Predictive Value of Tests, Primary Health Care, Proportional Hazards Models, Risk Assessment}, issn = {1552-5279}, doi = {10.1016/j.jalz.2013.11.006}, url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84893186546andpartnerID=40andmd5=3b617dce24578e022db389d90ad9ddd1}, author = {Deborah E Barnes and Alexa S. Beiser and Anne Lee and Kenneth M. Langa and Alain Koyama and Sarah R Preis and John Neuhaus and Ryan J McCammon and Kristine Yaffe and Seshadri, Sudha and Mary Haan and David R Weir} } @article {8926, title = {Economic development and gender inequality in cognition: a comparison of China and India, and of SAGE and the HRS sister studies.}, journal = {Journal of Economics of Ageing}, volume = {4}, year = {2014}, month = {2014 Dec 01}, pages = {114-125}, abstract = {

This paper examines cognition measures by age and gender from two types of studies in China and India. It finds that despite some notable differences in samples and measures, a general strong association of cognition in older ages with education emerges as a potential explanation for gender gaps and cohort differences. Female disadvantage in cognition is greater in India, both before and after controlling for education. The process of rural-urban migration draws more cognitively able women to cities in China but not in India. The advent of modern longitudinal studies of aging in these developing countries holds great promise for future work.

}, keywords = {CHARLS, Economics, Gender Differences, LASI, Older Adults, SAGE, Sister studies}, issn = {2212-828X}, doi = {10.1016/j.jeoa.2014.08.002}, author = {David R Weir and Margaret Lay and Kenneth M. Langa} } @article {8604, title = {Genetic diversity is a predictor of mortality in humans.}, journal = {BMC Genet}, volume = {15}, year = {2014}, month = {2014 Dec 29}, pages = {159}, abstract = {

BACKGROUND: It has been well-established, both by population genetics theory and direct observation in many organisms, that increased genetic diversity provides a survival advantage. However, given the limitations of both sample size and genome-wide metrics, this hypothesis has not been comprehensively tested in human populations. Moreover, the presence of numerous segregating small effect alleles that influence traits that directly impact health directly raises the question as to whether global measures of genomic variation are themselves associated with human health and disease.

RESULTS: We performed a meta-analysis of 17 cohorts followed prospectively, with a combined sample size of 46,716 individuals, including a total of 15,234 deaths. We find a significant association between increased heterozygosity and survival (P = 0.03). We estimate that within a single population, every standard deviation of heterozygosity an individual has over the mean decreases that person{\textquoteright}s risk of death by 1.57\%.

CONCLUSIONS: This effect was consistent between European and African ancestry cohorts, men and women, and major causes of death (cancer and cardiovascular disease), demonstrating the broad positive impact of genomic diversity on human survival.

}, keywords = {Genome-Wide Association Study, Heterozygote, Humans, Mortality, Polymorphism, Single Nucleotide, Proportional Hazards Models}, issn = {1471-2156}, doi = {10.1186/s12863-014-0159-7}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4301661/}, author = {Bihlmeyer, Nathan A and Brody, Jennifer A and Albert Vernon Smith and Kathryn L Lunetta and Michael A Nalls and Jennifer A Smith and Toshiko Tanaka and Gail Davies and Lei Yu and Saira S Mirza and Teumer, Alexander and Coresh, Josef and Pankow, James S and Franceschini, Nora and Scaria, Anish and Oshima, Junko and Psaty, Bruce M and Gudnason, Vilmundur and Gu{\dh}ny Eir{\'\i}ksd{\'o}ttir and Tamara B Harris and Li, Hanyue and Karasik, David and Douglas P Kiel and Melissa E Garcia and Yongmei Liu and Jessica Faul and Sharon L R Kardia and Wei Zhao and Luigi Ferrucci and Allerhand, Michael and David C Liewald and Redmond, Paul and John M Starr and Philip L de Jager and Nese Direk and Mohammed Arfan Ikram and Andr{\'e} G Uitterlinden and Homuth, Georg and Lorbeer, Roberto and Hans-J{\"o}rgen Grabe and Lenore J Launer and Joanne M Murabito and Andrew B Singleton and David R Weir and Bandinelli, Stefania and Ian J Deary and David A Bennett and Henning Tiemeier and Kocher, Thomas and Lumley, Thomas and Dan E Arking} } @article {9037, title = {The Health and Retirement Study: A Public Data Resource for Research on Aging}, journal = {Open Health Data}, volume = {2}, year = {2014}, month = {Apr-10-2015}, abstract = {The Health and Retirement Study (HRS) is a nationally representative longitudinal survey of more than 37,000 individuals in 23,000 households over age 50 in the United States. Fielded biennially since 1992, it was established to provide a national resource for data on the changing health and economic circumstances associated with aging. HRS covers four broad topic areas{\textemdash}income and wealth; health, cognition, and use of health care services; work and retirement; and family connections. HRS data are also linked at the individual level to administrative records from Social Security and Medicare, Veteran{\textquoteright}s Administration, the National Death Index, and employer-provided pension plan information. In 2006, data collection expanded to include biomarkers and genetics and greater depth in psychosocial well-being and social context. This blend of economic, health, and psychosocial information provides unprecedented potential to study increasingly complex questions about aging and retirement. HRS prioritizes rapid release of data while simultaneously protecting the confidentiality of respondents. Three categories of data{\textemdash}public, sensitive, and restricted{\textemdash}can be accessed through procedures described on the HRS website (hrsonline.isr.umich.edu).}, keywords = {Data methods, Survey Methodology}, issn = {2054-7102}, doi = {10.5334/ohd.am}, url = {http://openhealthdata.metajnl.com/articles/10.5334/ohd.am/}, author = {Amanda Sonnega and David R Weir} } @article {8065, title = {Health numeracy: the importance of domain in assessing numeracy.}, journal = {Med Decis Making}, volume = {34}, year = {2014}, month = {2014 Jan}, pages = {107-15}, publisher = {34}, abstract = {

BACKGROUND AND OBJECTIVE: Existing research concludes that measures of general numeracy can be used to predict individuals{\textquoteright} ability to assess health risks. We posit that the domain in which questions are posed affects the ability to perform mathematical tasks, raising the possibility of a separate construct of "health numeracy" that is distinct from general numeracy. The objective was to determine whether older adults{\textquoteright} ability to perform simple math depends on domain.

METHODS: Community-based participants completed 4 math questions posed in 3 different domains: a health domain, a financial domain, and a pure math domain. Participants were 962 individuals aged 55 and older, representative of the community-dwelling US population over age 54.

RESULTS: We found that respondents performed significantly worse when questions were posed in the health domain (54\% correct) than in either the pure math domain (66\% correct) or the financial domain (63\% correct). Our experimental measure of numeracy consisted of only 4 questions, and it is possible that the apparent effect of domain is specific to the mathematical tasks that these questions require.

CONCLUSIONS: These results suggest that health numeracy is strongly related to general numeracy but that the 2 constructs may not be the same. Further research is needed into how different aspects of general numeracy and health numeracy translate into actual medical decisions.

}, keywords = {Aged, Humans, Mathematics, Middle Aged, Self Efficacy, Surveys and Questionnaires, Task Performance and Analysis}, issn = {1552-681X}, doi = {10.1177/0272989X13493144}, url = {http://mdm.sagepub.com/content/34/1/107.abstract}, author = {Helen G Levy and Peter A. Ubel and Amanda J. Dillard and David R Weir and Angela Fagerlin} } @article {8056, title = {Identifying diabetics in Medicare claims and survey data: implications for health services research.}, journal = {BMC Health Serv Res}, volume = {14}, year = {2014}, note = {Export Date: 21 April 2014 Source: Scopus Article in Press}, month = {2014 Apr 03}, pages = {150}, publisher = {14}, abstract = {

BACKGROUND: Diabetes health services research often utilizes secondary data sources, including survey self-report and Medicare claims, to identify and study the diabetic population, but disagreement exists between these two data sources. We assessed agreement between the Chronic Condition Warehouse diabetes algorithm for Medicare claims and self-report measures of diabetes. Differences in healthcare utilization outcomes under each diabetes definition were also explored.

METHODS: Claims data from the Medicare Beneficiary Annual Summary File were linked to survey and blood data collected from the 2006 Health and Retirement Study. A Hemoglobin A1c reading, collected on 2,028 respondents, was used to reconcile discrepancies between the self-report and Medicare claims measures of diabetes. T-tests were used to assess differences in healthcare utilization outcomes for each diabetes measure.

RESULTS: The Chronic Condition Warehouse (CCW) algorithm yielded a higher rate of diabetes than respondent self-reports (27.3 vs. 21.2, p < 0.05). A1c levels of discordant claims-based diabetics suggest that these patients are not diabetic, however, they have high rates of healthcare spending and utilization similar to diabetics.

CONCLUSIONS: Concordance between A1c and self-reports was higher than for A1c and the CCW algorithm. Accuracy of self-reports was superior to the CCW algorithm. False positives in the claims data have similar utilization profiles to diabetics, suggesting minimal bias in some types of claims-based analyses, though researchers should consider sensitivity analysis across definitions for health services research.

}, keywords = {Aged, Aged, 80 and over, Algorithms, Diabetes Mellitus, Female, Glycated Hemoglobin, Health Services Research, Humans, Insurance Claim Review, Male, Medicare, Prevalence, United States}, issn = {1472-6963}, doi = {10.1186/1472-6963-14-150}, author = {Joseph W Sakshaug and David R Weir and Lauren Hersch Nicholas} } @article {8602, title = {Validation of blood-based assays using dried blood spots for use in large population studies.}, journal = {Biodemography Soc Biol}, volume = {60}, year = {2014}, month = {2014}, pages = {38-48}, abstract = {

Assessment of health in large population studies has increasingly incorporated measures of blood-based biomarkers based on the use of dried blood spots (DBS). The validity of DBS assessments made by labs used by large studies is addressed by comparing assay values from DBS collected using conditions similar to those used in the field with values from whole blood samples. The DBS approach generates values that are strongly related to whole blood levels of HbA1c, cystatin C, and C-reactive protein. Assessing lipid levels reliably with DBS appears to be a greater challenge. However, even when DBS values and values from venous blood are highly correlated, they are often on a different scale, and using conventional cutoffs may be misleading.

}, keywords = {Biomarkers, C-reactive protein, Cholesterol, Cholesterol, HDL, Cystatin C, Dried Blood Spot Testing, Glycated Hemoglobin A, Humans, Middle Aged, Reference Values, Reproducibility of Results}, issn = {1948-5573}, doi = {10.1080/19485565.2014.901885}, url = {http://www.tandfonline.com/doi/abs/10.1080/19485565.2014.901885}, author = {Eileen M. Crimmins and Jung K Kim and Heather McCreath and Jessica Faul and David R Weir and Teresa Seeman} } @article {5954, title = {Documentation of Biomarkers in the 2006 and 2008 Health and Retirement Study}, year = {2013}, institution = {Institute for Social Research, University of Michigan}, address = {Ann Arbor, Michigan}, abstract = {Biomarkers refer to the general range of physiological, metabolic, biochemical, endocrine and genetic measures that can be obtained in living organisms. The term is most commonly used to refer to one-time biochemical or hematological measures made on blood or other available bodily fluids, but perhaps the term should be used for a broader range of measures. In 2006 and 2008, HRS included the following biomarkers measurements, administered in this order: Saliva collection for DNA extraction; Blood spot collection for cholesterol, hemoglobin A1C, CRP and cystatin C analysis (results for C-reactive protein and cystatin C are forthcoming). This report describes the following for each of the measures listed above: Rationale and key citations; Sample description; Measure description; Equipment; Protocol description; Special instructions.}, keywords = {Health Conditions and Status, Healthcare, Methodology}, author = {Eileen M. Crimmins and Jessica Faul and Jung K Kim and Heidi M Guyer and Kenneth M. Langa and Mary Beth Ofstedal and Amanda Sonnega and Robert B Wallace and David R Weir} } @article {8608, title = {Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations.}, journal = {Am J Hum Genet}, volume = {93}, year = {2013}, month = {2013 Sep 05}, pages = {545-54}, abstract = {

High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0~{\texttimes} 10(-8)) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability.

}, keywords = {Africa, African Continental Ancestry Group, Blood pressure, Cohort Studies, Databases, Genetic, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, Reproducibility of Results}, issn = {1537-6605}, doi = {10.1016/j.ajhg.2013.07.010}, author = {Franceschini, Nora and Fox, Ervin and Zhang, Zhaogong and Edwards, Todd L and Michael A Nalls and Yun Ju Sung and Bamidele O Tayo and Yan V Sun and Gottesman, Omri and Adebawole Adeyemo and Andrew D Johnson and Young, J Hunter and Kenneth Rice and Duan, Qing and Chen, Fang and Yun Li and Tang, Hua and Myriam Fornage and Keene, Keith L and Andrews, Jeanette S and Jennifer A Smith and Jessica Faul and Guangfa, Zhang and Guo, Wei and Liu, Yu and Murray, Sarah S and Musani, Solomon K and Srinivasan, Sathanur and Digna R Velez Edwards and Wang, Heming and Becker, Lewis C and Bovet, Pascal and Bochud, Murielle and Broeckel, Ulrich and Burnier, Michel and Carty, Cara and Daniel I Chasman and Georg B Ehret and Chen, Wei-Min and Chen, Guanjie and Wei Chen and Ding, Jingzhong and Dreisbach, Albert W and Michele K Evans and Guo, Xiuqing and Melissa E Garcia and Jensen, Rich and Keller, Margaux F and Lettre, Guillaume and Lotay, Vaneet and Martin, Lisa W and Moore, Jason H and Alanna C Morrison and Thomas H Mosley and Ogunniyi, Adesola and Walter R Palmas and George J Papanicolaou and Alan Penman and Polak, Joseph F and Ridker, Paul M and Babatunde Salako and Andrew B Singleton and Daniel Shriner and Kent D Taylor and Ramachandran S Vasan and Kerri Wiggins and Williams, Scott M and Yanek, Lisa R and Wei Zhao and Alan B Zonderman and Becker, Diane M and Berenson, Gerald and Boerwinkle, Eric and Erwin P Bottinger and Cushman, Mary and Charles B Eaton and Nyberg, Fredrik and Gerardo Heiss and Joel N Hirschhron and Howard, Virginia J and Karczewsk, Konrad J and Lanktree, Matthew B and Liu, Kiang and Yongmei Liu and Ruth J F Loos and Margolis, Karen and Snyder, Michael and Psaty, Bruce M and Schork, Nicholas J and David R Weir and Charles N Rotimi and Sale, Michele M and Tamara B Harris and Sharon L R Kardia and Hunt, Steven C and Donna K Arnett and Redline, Susan and Cooper, Richard S and Neil Risch and Rao, D C and Rotter, Jerome I and Chakravarti, Aravinda and Reiner, Alex P and Levy, Daniel and Keating, Brendan J and Zhu, Xiaofeng} } @article {8620, title = {GWAS of 126,559 individuals identifies genetic variants associated with educational attainment.}, journal = {Science}, volume = {340}, year = {2013}, month = {2013 Jun 21}, pages = {1467-71}, abstract = {

A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R(2) ≈ 0.02\%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for ≈2\% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.

}, keywords = {Cognition, Educational Status, Endophenotypes, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Multifactorial Inheritance, Polymorphism, Single Nucleotide}, issn = {1095-9203}, doi = {10.1126/science.1235488}, author = {Cornelius A Rietveld and Sarah E Medland and Derringer, Jaime and Yang, Jian and T{\~o}nu Esko and Martin, Nicolas W and Westra, Harm-Jan and Shakhbazov, Konstantin and Abdel Abdellaoui and Agrawal, Arpana and Albrecht, Eva and Alizadeh, Behrooz Z and Amin, Najaf and Barnard, John and Baumeister, Sebastian E and Benke, Kelly S and Bielak, Lawrence F and Boatman, Jeffrey A and Patricia A. Boyle and Gail Davies and Christiaan de Leeuw and Eklund, Niina and Daniel S Evans and Rudolf Ferhmann and Fischer, Krista and Gieger, Christian and Gjessing, H{\r a}kon K and H{\"a}gg, Sara and Harris, Jennifer R and Caroline Hayward and Holzapfel, Christina and Carla A Ibrahim-Verbaas and Ingelsson, Erik and Jacobsson, Bo and Joshi, Peter K and Jugessur, Astanand and Marika A Kaakinen and Kanoni, Stavroula and Karjalainen, Juha and Kolcic, Ivana and Kristiansson, Kati and Kutalik, Zolt{\'a}n and J. Lahti and Lee, Sang H and Lin, Peng and Penelope A Lind and Yongmei Liu and Kurt Lohman and Loitfelder, Marisa and McMahon, George and Vidal, Pedro Marques and Osorio Meirelles and Lili Milani and Myhre, Ronny and Nuotio, Marja-Liisa and Christopher J Oldmeadow and Katja E Petrovic and Wouter J Peyrot and Polasek, Ozren and Quaye, Lydia and Reinmaa, Eva and Rice, John P and Rizzi, Thais S and Schmidt, Helena and Schmidt, Reinhold and Albert Vernon Smith and Jennifer A Smith and Toshiko Tanaka and Antonio Terracciano and van der Loos, Matthijs J H M and Vitart, Veronique and V{\"o}lzke, Henry and J{\"u}rgen Wellmann and Lei Yu and Wei Zhao and Allik, J{\"u}ri and John R. Attia and Bandinelli, Stefania and Bastardot, Fran{\c c}ois and Jonathan P. Beauchamp and David A Bennett and Klaus Berger and Laura Bierut and Dorret I Boomsma and B{\"u}ltmann, Ute and Campbell, Harry and Chabris, Christopher F and Cherkas, Lynn and Chung, Mina K and Francesco Cucca and de Andrade, Mariza and Philip L de Jager and De Neve, Jan-Emmanuel and Ian J Deary and George Dedoussis and Deloukas, Panos and Dimitriou, Maria and Gu{\dh}ny Eir{\'\i}ksd{\'o}ttir and Elderson, Martin F and Johan G Eriksson and Jessica Faul and Luigi Ferrucci and Melissa E Garcia and Gr{\"o}nberg, Henrik and Gu{\dh}nason, Vilmundur and Hall, Per and Harris, Juliette M and Tamara B Harris and Nicholas D Hastie and Andrew C Heath and Dena G Hernandez and Hoffmann, Wolfgang and Hofman, Adriaan and Holle, Rolf and Holliday, Elizabeth G and Jouke-Jan Hottenga and Iacono, William G and Illig, Thomas and J{\"a}rvelin, Marjo-Riitta and K{\"a}h{\"o}nen, Mika and Kaprio, Jaakko and Kirkpatrick, Robert M and Kowgier, Matthew and Latvala, Antti and Lenore J Launer and Lawlor, Debbie A and Lehtim{\"a}ki, Terho and Li, Jingmei and Paul Lichtenstein and Lichtner, Peter and David C Liewald and Pamela A F Madden and Patrik K E Magnusson and M{\"a}kinen, Tomi E and Masala, Marco and McGue, Matt and Andres Metspalu and Mielck, Andreas and Michael B Miller and Grant W Montgomery and Mukherjee, Sutapa and Nyholt, Dale R and Ben A Oostra and Palmer, Lyle J and Aarno Palotie and Brenda W J H Penninx and Markus Perola and Peyser, Patricia A and Preisig, Martin and Katri R{\"a}ikk{\"o}nen and Olli T Raitakari and Realo, Anu and Ring, Susan M and Ripatti, Samuli and Fernando Rivadeneira and Rudan, Igor and Rustichini, Aldo and Veikko Salomaa and Sarin, Antti-Pekka and Schlessinger, David and Rodney J Scott and Snieder, Harold and St Pourcain, Beate and John M Starr and Sul, Jae Hoon and Surakka, Ida and Svento, Rauli and Teumer, Alexander and Henning Tiemeier and van Rooij, Frank J A and Van Wagoner, David R and Vartiainen, Erkki and Viikari, Jorma and Vollenweider, Peter and Vonk, Judith M and Waeber, G{\'e}rard and David R Weir and Wichmann, H-Erich and Elisabeth Widen and Gonneke Willemsen and James F Wilson and Alan F Wright and Dalton C Conley and Davey-Smith, George and Lude L Franke and Groenen, Patrick J F and Hofman, Albert and Johannesson, Magnus and Sharon L R Kardia and Krueger, Robert F and David I Laibson and Nicholas G Martin and Meyer, Michelle N and Posthuma, Danielle and A. Roy Thurik and Nicholas J Timpson and Andr{\'e} G Uitterlinden and Cornelia M van Duijn and Peter M Visscher and Daniel J. Benjamin and Cesarini, David and Philipp D Koellinger} } @article {5959, title = {New Measures of Fluid Intelligence in the HRS}, year = {2013}, institution = {Institute for Social Research, University of Michigan}, address = {Ann Arbor, Michigan}, abstract = {This user guide describes how measures designed to test quantitative reasoning, verbal reasoning and verbal fluency were implemented in the 2010 and 2012 waves of the Health and Retirement Study. The Number Series test and Retrieval Fluency test were administered in the 2010 and 2012 waves of HRS to the full sample. The Verbal Analogies test was administered to a 10 percent random sample of the full HRS sample in 2012. Number Series measures quantitative reasoning, a specific type of fluid cognitive ability or fluid intelligence. Quantitative reasoning ability involves reasoning with concepts that depend upon mathematical relationships. The number series task requires the respondent to look at a series of numbers with a number missing from the series. The respondent must determine the numerical pattern and then provide the missing number in the series. Retrieval Fluency measures an aspect of long-term retrieval : fluency of retrieval from stored knowledge. It was first incorporated in the HRS in the 2010 wave . This test is a typical neuropsychology test and was adapted by McArdle and Woodcock from the WJ-III Tests of Achievement: Retrieval Fluency ( Riverside Publishing). The measure consisted of a single item in which respondents were asked to name as many animals as they could within a 60-second time limit. This measure is consistent with animal fluency measures commonly administered in other neuropsychological exams (e.g., the CERAD animal fluency measure; Morris et al., 1989) . Administration protocols, test scoring, and data quality review procedures are discussed for each measure.}, keywords = {Health Conditions and Status, Methodology}, author = {Gwenith G Fisher and John J McArdle and Ryan J McCammon and Amanda Sonnega and David R Weir} } @article {8515, title = {Psychosocial and Lifestyle Questionnaire 2006 - 2010: Documentation Report}, year = {2013}, month = {02/2013}, pages = {62}, institution = {Survey Research Center, Institute for Social Research, University of Michigan}, address = {Ann Arbor}, abstract = {In 2004, HRS piloted a new feature for data collection in the form of self-administered questionnaires that were left with respondents upon the completion of an in-person Core Interview. Since 2006, this mode of data collection has been utilized to obtain information about participants{\textquoteright} evaluations of their life circumstances, subjective wellbeing, and lifestyle. This psychosocial information is obtained in each biennial wave from a rotating (random) 50\% of the core panel participants who complete the enhanced face-to-face interview (EFTF). Longitudinal data will be available at four-year intervals: the 2010 wave provides the first longitudinal psychosocial data from the 2006 participants. Some longitudinal data is also available for the 2004 participants in subsequent waves. Electronic versions of the HRS Participant (Psychosocial) Lifestyle Questionnaires used in the 2004 pilot, and the 2006, 2008, and 2010 waves are available on the HRS website (Documentation/Questionnaires - scroll down to the end of the Biennial Content to Psychosocial - Section LB). Because the questionnaire was left with respondents at the end of the EFTF interview for them to complete and mail back to study offices, the questionnaire came to be known and is referred to on the HRS website as the LeaveBehind (LB). We use the terms Participant Lifestyle Questionnaire and Leave-Behind (or LB) in this report to refer to the self-administered psychosocial data collection.}, keywords = {Data collection, Meta-analyses, Psychosocial, Question Characteristics}, author = {Jacqui Smith and Gwenith G Fisher and Lindsay H Ryan and Philippa J Clarke and House, Jim and David R Weir} } @article {8943, title = {Linking Survey and Administrative Records: Mechanisms of Consent}, journal = {Sociological Methods \& Research}, volume = {41}, year = {2012}, month = {2012 Nov}, pages = {535-569}, abstract = {

Survey records are increasingly being linked to administrative databases to enhance the survey data and increase research opportunities for data users. A necessary prerequisite to linking survey and administrative records is obtaining informed consent from respondents. Obtaining consent from all respondents is a difficult challenge and one that faces significant resistance. Consequently, data linkage consent rates vary widely from study-to-study. Several studies have found significant differences between consenters and non-consenters on socio-demographic variables, but no study has investigated the underlying mechanisms of consent from a theory-driven perspective. In this study, we describe and test several hypotheses related to respondents{\textquoteright} willingness to consent to an earnings and benefit data linkage request based on mechanisms related to financial uncertainty, privacy concerns, resistance towards the survey interview, level of attentiveness during the interview, the respondents{\textquoteright} preexisting relationship with the administrative data agency, and matching respondents and interviewers on observable characteristics. The results point to several implications for survey practice and suggestions for future research.

}, keywords = {Consent, Meta-analyses, Survey Methodology}, issn = {0049-1241}, doi = {10.1177/0049124112460381}, author = {Joseph W Sakshaug and Mick P. Couper and Mary Beth Ofstedal and David R Weir} } @article {5947, title = {Personality Traits and Economic Preparation for Retirement}, number = {wp279}, year = {2012}, institution = {Michigan Retirement and Disability Research Center, University of Michigan}, address = {Ann Arbor, MI}, abstract = {This paper assesses the effects of personality traits on economic preparation for retirement, wealth accumulation, and consumption, among persons 66 to 69 years of age. Among the five chief personality traits of neuroticism, extroversion, agreeableness, conscientiousness, and openness, we focus most on conscientiousness. We find levels of adequate economic preparation for retirement ranging from 29 percent to 90 percent and that conscientiousness positively affects the proportion of persons adequately prepared for retirement, while neuroticism negatively affects it. Both consumption and wealth increase with conscientiousness but wealth increases faster, indicating that more conscientious persons save more out of retirement resources.}, keywords = {Consumption and Savings, Health Conditions and Status, Net Worth and Assets, Retirement Planning and Satisfaction}, url = {https://ideas.repec.org/p/mrr/papers/wp279.html}, author = {Michael D Hurd and Angela Lee Duckworth and Susann Rohwedder and David R Weir} } @article {7700, title = {Unexpected retirement from full time work after age 62: consequences for life satisfaction in older Americans}, journal = {European Journal of Ageing}, volume = {9}, year = {2012}, note = {Times Cited: 1}, pages = {207-219}, publisher = {9}, abstract = {Recent policy shifts in the United States have resulted in an increase in the number of older workers remaining in the labor force. Increases in the retirement age for receiving full Social Security benefits coupled with declining pension funds and the erosion of employer retiree health benefits, mean that current cohorts of older workers may fully expect to work longer than previous generations. Yet, working longer may not always be possible due to health problems, outdated skills, economic insecurity, and competing obligations. We examine the consequences of unmet expectations for full time work after age 62 for life satisfaction in a nationally representative sample of older Americans. With longitudinal data from the Health and Retirement Study (1998-2008), this paper uses repeated measures of expectations for later life work among a cohort of Americans (N = 1684) gathered prospectively over an 8-year period, and examines the effects of unfulfilled expectations on subsequent life satisfaction. Using generalized growth mixture modeling three latent classes of individuals were identified with distinct trajectories of later life work expectations (low expectations, high expectations, and neutral expectations for full time work after age 62). A majority of men had generally high expectations to work full time past age 62, whereas the majority of women reported a low probability of working full time after age 62. When comparing expectations to actual full time work past age 62, we found no effects of unmet expectations for women. However, men with less job stability (reflected by shorter job tenure and lower incomes) generally had high expectations to work longer, and their life satisfaction scores were significantly lower when these expectations were not realized. The hazards of missed expectations for later life work have consequences for subjective well-being in older adults.}, keywords = {Demographics, Employment and Labor Force, Event History/Life Cycle, Expectations}, doi = {10.1007/s10433-012-0229-5}, author = {Philippa J Clarke and Marshall, Victor W. and David R Weir} } @article {9038, title = {Who does well in life? Conscientious adults excel in both objective and subjective success.}, journal = {Frontiers in Psychology}, volume = {3}, year = {2012}, month = {2012}, pages = {356}, abstract = {This article investigates how personality and cognitive ability relate to measures of objective success (income and wealth) and subjective success (life satisfaction, positive affect, and lack of negative affect) in a representative sample of 9,646 American adults. In cross-sectional analyses controlling for demographic covariates, cognitive ability, and other Big Five traits, conscientiousness demonstrated beneficial associations of small-to-medium magnitude with all success outcomes. In contrast, other traits demonstrated stronger, but less consistently beneficial, relations with outcomes in the same models. For instance, emotional stability demonstrated medium-to-large associations with life satisfaction and affect but a weak association with income and no association with wealth. Likewise, extraversion demonstrated medium-to-large associations with positive affect and life satisfaction but small-to-medium associations with wealth and (lack of) negative affect and no association with income. Cognitive ability showed small-to-medium associations with income and wealth but no association with any aspect of subjective success. More agreeable adults were worse off in terms of objective success and life satisfaction, demonstrating small-to-medium inverse associations with those outcomes, but they did not differ from less agreeable adults in positive or negative affect. Likewise, openness to experience demonstrated small-to-medium inverse associations with every success outcome except positive affect, in which more open adults were slightly higher. Notably, in each of the five models predicting objective and subjective success outcomes, individual differences other than conscientiousness explained more variance than did conscientiousness. Thus, the benefits of conscientiousness may be remarkable more for their ubiquity than for their magnitude.}, keywords = {Conscientiousness, Success}, issn = {1664-1078}, doi = {10.3389/fpsyg.2012.00356}, author = {Angela Lee Duckworth and David R Weir and Tsukayama, Eli and Kwok, David} } @article {7631, title = {Assessment of cognition using surveys and neuropsychological assessment: the Health and Retirement Study and the Aging, Demographics, and Memory Study.}, journal = {J Gerontol B Psychol Sci Soc Sci}, volume = {66 Suppl 1}, year = {2011}, note = {Crimmins, Eileen M Kim, Jung Ki Langa, Kenneth M Weir, David R P30 AG17265/AG/NIA NIH HHS/United States U01 AG009740/AG/NIA NIH HHS/United States Research Support, N.I.H., Extramural United States The journals of gerontology. Series B, Psychological sciences and social sciences J Gerontol B Psychol Sci Soc Sci. 2011 Jul;66 Suppl 1:i162-71.}, month = {2011 Jul}, pages = {i162-71}, publisher = {66 Suppl 1}, abstract = {

OBJECTIVES: This study examines the similarity of cognitive assessments using 1 interview in a large population study, the Health and Retirement Study (HRS), and a subsample in which a detailed neuropsychiatric assessment has been performed (Aging, Demographics, and Memory Study [ADAMS]).

METHODS: Respondents are diagnosed in ADAMS as demented, cognitively impaired without dementia (CIND), or as having normal cognitive function. Multinomial logistic analysis is used to predict diagnosis using a variety of cognitive and noncognitive measures from the HRS and additional measures and information from ADAMS.

RESULTS: The cognitive tests in HRS predict the ADAMS diagnosis in 74\% of the sample able to complete the HRS survey on their own. Proxy respondents answer for a large proportion of HRS respondents who are diagnosed as demented in ADAMS. Classification of proxy respondents with some cognitive impairment can be predicted in 86\% of the sample. Adding a small number of additional tests from ADAMS can increase each of these percentages to 84\% and 93\%, respectively.

DISCUSSION: Cognitive assessment appropriate for diagnosis of dementia and CIND in large population surveys could be improved with more targeted information from informants and additional cognitive tests targeting other areas of brain function.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Cognition, Cognition Disorders, Dementia, Educational Status, Female, Humans, Interviews as Topic, Logistic Models, Longitudinal Studies, Male, Multivariate Analysis, Neuropsychological tests, Odds Ratio, Prevalence, Sex Factors, United States}, issn = {1758-5368}, doi = {10.1093/geronb/gbr048}, author = {Eileen M. Crimmins and Jung K Kim and Kenneth M. Langa and David R Weir} } @article {7561, title = {Do biological measures mediate the relationship between education and health: A comparative study.}, journal = {Soc Sci Med}, volume = {72}, year = {2011}, month = {2011 Jan}, pages = {307-15}, publisher = {72}, abstract = {

Despite a myriad of studies examining the relationship between socioeconomic status and health outcomes, few have assessed the extent to which biological markers of chronic disease account for social disparities in health. Studies that have examined this issue have generally been based on surveys in wealthy countries that include a small set of clinical markers of cardiovascular disease. The availability of recent data from nationally representative surveys of older adults in Costa Rica and Taiwan that collected a rich set of biomarkers comparable to those in a recent US survey permits us to explore these associations across diverse populations. Similar regression models were estimated on three data sets - the Social Environment and Biomarkers of Aging Study in Taiwan, the Costa Rican Study on Longevity and Healthy Aging, and the Health and Retirement Study in the USA - in order to assess (1) the strength of the associations between educational attainment and a broad range of biomarkers; and (2) the extent to which these biomarkers account for the relationships between education and two measures of health status (self-rated health, functional limitations) in older populations. The estimates suggest non-systematic and weak associations between education and high risk biomarker values in Taiwan and Costa Rica, in contrast to generally negative and significant associations in the US, especially among women. The results also reveal negligible or modest contributions of the biomarkers to educational disparities in the health outcomes. The findings are generally consistent with previous research suggesting stronger associations between socioeconomic status and health in wealthy countries than in middle-income countries and may reflect higher levels of social stratification in the US. With access to an increasing number of longitudinal biosocial surveys, researchers may be better able to distinguish true variations in the relationship between socioeconomic status and health across different settings from methodological differences.

}, keywords = {Biomarkers, Blood pressure, Body Mass Index, Cholesterol, Costa Rica, Educational Status, Female, Health Status Disparities, Health Status Indicators, Health Surveys, Humans, Male, Middle Aged, Qualitative Research, Taiwan, United States}, issn = {1873-5347}, doi = {10.1016/j.socscimed.2010.11.004}, author = {Goldman, Noreen and Cassio M. Turra and Rosero-Bixby, Luis and David R Weir and Eileen M. Crimmins} } @article {7586, title = {Incidence of dementia and cognitive impairment, not dementia in the United States.}, journal = {Ann Neurol}, volume = {70}, year = {2011}, month = {2011 Sep}, pages = {418-26}, abstract = {

OBJECTIVE: Estimates of incident dementia, and cognitive impairment, not dementia (CIND) (or the related mild cognitive impairment) are important for public health and clinical care policy. In this paper, we report US national incidence rates for dementia and CIND.

METHODS: Participants in the Aging, Demographic, and Memory Study (ADAMS) were evaluated for cognitive impairment using a comprehensive in-home assessment. A total of 456 individuals aged 72 years and older, who were not demented at baseline, were followed longitudinally from August 2001 to December 2009. An expert consensus panel assigned a diagnosis of normal cognition, CIND, or dementia and its subtypes. Using a population-weighted sample, we estimated the incidence of dementia, Alzheimer disease (AD), vascular dementia (VaD), and CIND by age. We also estimated the incidence of progression from CIND to dementia.

RESULTS: The incidence of dementia was 33.3 (standard error [SE], 4.2) per 1,000 person-years and 22.9 (SE, 2.9) per 1,000 person-years for AD. The incidence of CIND was 60.4 (SE, 7.2) cases per 1,000 person-years. An estimated 120.3 (SE, 16.9) individuals per 1,000 person-years progressed from CIND to dementia. Over a 5.9-year period, about 3.4 million individuals aged 72 and older in the United States developed incident dementia, of whom approximately 2.3 million developed AD, and about 637,000 developed VaD. Over this same period, almost 4.8 million individuals developed incident CIND.

INTERPRETATION: The incidence of CIND is greater than the incidence of dementia, and those with CIND are at high risk of progressing to dementia, making CIND a potentially valuable target for treatments aimed at slowing cognitive decline.

}, keywords = {Aged, Aged, 80 and over, Alzheimer disease, Cognition Disorders, Cohort Studies, Dementia, Diagnostic and Statistical Manual of Mental Disorders, disease progression, Female, Humans, Logistic Models, Longitudinal Studies, Male, Models, Statistical, United States}, issn = {1531-8249}, doi = {10.1002/ana.22362}, author = {Brenda L Plassman and Kenneth M. Langa and Ryan J McCammon and Gwenith G Fisher and Guy G Potter and James R Burke and David C Steffens and Norman L Foster and Bruno J Giordani and Frederick W Unverzagt and Kathleen A Welsh-Bohmer and Steven G Heeringa and David R Weir and Robert B Wallace} } @article {5918, title = {Personality and Response to the Financial Crisis}, number = {UM11-09}, year = {2011}, institution = {The University of Michigan}, address = {Ann Arbor, MI}, abstract = {In a previous study, we found the family of personality traits known as conscientiousness to be associated in cross-sectional analyses with both lifetime earnings and wealth. In this study, we used data from an Internet survey of HRS respondents in the second quarter of 2009 to test whether conscientiousness and other Big Five factors prospectively predicted responses to the financial crisis of 2008/09. In addition, to improve the targeting and design of behavioral interventions for at-risk individuals, we examined two specific facets of conscientiousness (i.e., self-control and perseverance) that may be more highly related to these economic outcomes than other facets. Finally, we used data from the Consumption and Activities Mail Survey (CAMS) to examine whether personality is related to the proportion of income saved vs. spent. Missing data precluded sufficiently powerful prospective analyses of personality and responses to the financial crisis. Likewise, data on self-control and perseverance from the 2010 experimental module were not sufficient at the time of final reporting to come to definitive conclusions about how these facets relate to economic outcomes. We did find that conscientious adults save more and spend less of their incomes, whereas adults who are higher in openness to experience (e.g., adventurous, sophisticated) save less and spend more of their income. The robust associations between conscientiousness and economic outcomes suggests further investigation of interventions that improve conscientiousness as well as policies that specifically target less conscientious individuals (e.g., default choices for retirement savings).}, keywords = {Health Conditions and Status, Net Worth and Assets, Public Policy}, url = {https://mrdrc.isr.umich.edu/projects/personality-and-response-to-the-financial-crisis/}, author = {Angela Lee Duckworth and David R Weir} } @article {7652, title = {Proxy interviews and bias in the distribution of cognitive abilities due to non-response in longitudinal studies: a comparison of HRS and ELSA.}, journal = {Longit Life Course Stud}, volume = {2}, year = {2011}, month = {2011 May}, pages = {170-184}, publisher = {2}, issn = {1757-9597}, doi = {10.14301/llcs.v2i2.116}, author = {David R Weir and Jessica Faul and Kenneth M. Langa} } @article {7647, title = {Recruitment and retention of minority participants in the health and retirement study.}, journal = {Gerontologist}, volume = {51 Suppl 1}, year = {2011}, note = {Ofstedal, Mary B Weir, David R U01AG009740/AG/NIA NIH HHS/United States Comparative Study Research Support, N.I.H., Extramural United States The Gerontologist Gerontologist. 2011 Jun;51 Suppl 1:S8-20.}, month = {2011 Jun}, pages = {S8-20}, publisher = {51 Suppl 1}, abstract = {

PURPOSE: Minority oversamples of African Americans and Hispanics have been a key feature of the Health and Retirement Study (HRS) design from its origins in 1992. The objective of this article was to assess the quality of the HRS with respect to the recruitment and retention of minority respondents.

DESIGN AND METHODS: To evaluate minority recruitment efforts, we examine baseline response rates for the early baby boom cohort that was added in the 2004 wave and the representativeness of this cohort with regard to demographic, socioeconomic, and health characteristics. To evaluate retention, we focus on minority differentials in 2008 interview, nonresponse and mortality outcomes for the full HRS sample. We also examine minority differentials in participation in supplemental components of the HRS.

RESULTS: Minority response rates at baseline and in longitudinal follow-ups for the main HRS interview have been equal to or better than that of majority Whites. Conversely, response rates to some specific supplemental components have been lower for minority sample members.

IMPLICATIONS: The oversample strategies that the HRS has employed have been successful at identifying and recruiting minority participants at response rates very comparable with that of Whites and others. Minority differentials in participation in supplemental components have been overcome to some extent through interviewer training and targeted follow-up strategies. The HRS experience suggests that well-trained interviewers can overcome most if not all of whatever race and ethnic differentials exist in willingness to participate in surveys, including those involving biological data collection.

}, keywords = {Aged, Biomarkers, Black or African American, Female, Health Promotion, Health Surveys, Hispanic or Latino, Humans, Male, Middle Aged, Minority Groups, Minority health, National Health Programs, Patient Dropouts, Patient Selection, Retirement, Sampling Studies, Surveys and Questionnaires, United States}, issn = {1758-5341}, doi = {10.1093/geront/gnq100}, author = {Mary Beth Ofstedal and David R Weir} } @article {7566, title = {Reducing case ascertainment costs in U.S. population studies of Alzheimer{\textquoteright}s disease, dementia, and cognitive impairment-Part 1.}, journal = {Alzheimers Dement}, volume = {7}, year = {2011}, month = {2011 Jan}, pages = {94-109}, publisher = {7}, abstract = {

Establishing methods for ascertainment of dementia and cognitive impairment that are accurate and also cost-effective is a challenging enterprise. Large population-based studies often using administrative data sets offer relatively inexpensive and reliable estimates of severe conditions including moderate to advanced dementia that are useful for public health planning, but they can miss less severe cognitive impairment which may be the most effective point for intervention. Clinical and epidemiological cohorts, intensively assessed, provide more sensitive detection of less severe cognitive impairment but are often costly. In this article, several approaches to ascertainment are evaluated for validity, reliability, and cost. In particular, the methods of ascertainment from the Health and Retirement Study are described briefly, along with those of the Aging, Demographics, and Memory Study (ADAMS). ADAMS, a resource-intense sub-study of the Health and Retirement Study, was designed to provide diagnostic accuracy among persons with more advanced dementia. A proposal to streamline future ADAMS assessments is offered. Also considered are algorithmic and Web-based approaches to diagnosis that can reduce the expense of clinical expertise and, in some contexts, can reduce the extent of data collection. These approaches are intended for intensively assessed epidemiological cohorts where goal is valid and reliable case detection with efficient and cost-effective tools.

}, keywords = {Aging, Algorithms, Alzheimer disease, Cognition Disorders, Community Health Planning, Cost-Benefit Analysis, Dementia, Health Surveys, Humans, Internet, Reproducibility of Results, United States}, issn = {1552-5279}, doi = {10.1016/j.jalz.2010.11.004}, url = {http://mgetit.lib.umich.edu/sfx_local?ctx_enc=info 3Aofi 2Fenc 3AUTF-8;ctx_id=10_1;ctx_tim=2011-03-28T16 3A26 3A0EDT;ctx_ver=Z39.88-2004;rfr_id=info 3Asid 2Fsfxit.com 3Acitation;rft.genre=article;rft_id=info 3Apmid 2F21255747;rft_val_fmt=info 3Aofi 2Ffmt }, author = {David R Weir and Robert B Wallace and Kenneth M. Langa and Brenda L Plassman and Robert S Wilson and David A Bennett and Duara, Ranjan and Loewenstein, David and Ganguli, Mary and Sano, Mary} } @article {7687, title = {Regional variation in the association between advance directives and end-of-life Medicare expenditures.}, journal = {JAMA}, volume = {306}, year = {2011}, month = {2011 Oct 05}, pages = {1447-53}, publisher = {112}, abstract = {

CONTEXT: It is unclear if advance directives (living wills) are associated with end-of-life expenditures and treatments.

OBJECTIVE: To examine regional variation in the associations between treatment-limiting advance directive use, end-of-life Medicare expenditures, and use of palliative and intensive treatments.

DESIGN, SETTING, AND PATIENTS: Prospectively collected survey data from the Health and Retirement Study for 3302 Medicare beneficiaries who died between 1998 and 2007 linked to Medicare claims and the National Death Index. Multivariable regression models examined associations between advance directives, end-of-life Medicare expenditures, and treatments by level of Medicare spending in the decedent{\textquoteright}s hospital referral region.

MAIN OUTCOME MEASURES: Medicare expenditures, life-sustaining treatments, hospice care, and in-hospital death over the last 6 months of life.

RESULTS: Advance directives specifying limits in care were associated with lower spending in hospital referral regions with high average levels of end-of-life expenditures (-$5585 per decedent; 95\% CI, -$10,903 to -$267), but there was no difference in spending in hospital referral regions with low or medium levels of end-of-life expenditures. Directives were associated with lower adjusted probabilities of in-hospital death in high- and medium-spending regions (-9.8\%; 95\% CI, -16\% to -3\% in high-spending regions; -5.3\%; 95\% CI, -10\% to -0.4\% in medium-spending regions). Advance directives were associated with higher adjusted probabilities of hospice use in high- and medium-spending regions (17\%; 95\% CI, 11\% to 23\% in high-spending regions, 11\%; 95\% CI, 6\% to 16\% in medium-spending regions), but not in low-spending regions.

CONCLUSION: Advance directives specifying limitations in end-of-life care were associated with significantly lower levels of Medicare spending, lower likelihood of in-hospital death, and higher use of hospice care in regions characterized by higher levels of end-of-life spending.

}, keywords = {Advance directives, Aged, Aged, 80 and over, Data collection, Female, Health Expenditures, Hospice Care, Hospital Mortality, Hospitals, Humans, Kidney Failure, Chronic, Male, Medicare, Palliative care, Prospective Studies, Regression Analysis, Terminal Care, United States}, issn = {1538-3598}, doi = {10.1001/jama.2011.1410}, url = {http://proquest.umi.com.proxy.lib.umich.edu/pqdweb?did=2590187421andFmt=7andclientId=17822andRQT=309andVName=PQD}, author = {Lauren Hersch Nicholas and Kenneth M. Langa and Theodore J Iwashyna and David R Weir} } @article {7565, title = {Sources of variability in estimates of the prevalence of Alzheimer{\textquoteright}s disease in the United States.}, journal = {Alzheimers Dement}, volume = {7}, year = {2011}, month = {2011 Jan}, pages = {74-9}, publisher = {7}, abstract = {

BACKGROUND: The prevalence of Alzheimer{\textquoteright}s disease (AD) in the United States was estimated at 2.3 million in 2002 by the Aging, Demographics, and Memory Study (ADAMS), which is almost 50\% less than the estimate of 4.5 million in 2000 derived from the Chicago Health and Aging Project.

METHODS: We considered how differences in diagnostic criteria may have contributed to these differences in AD prevalence.

RESULTS: We identified several important differences in diagnostic criteria that may have contributed to the differing estimates of AD prevalence. Two factors were especially noteworthy. First, the Diagnostic and Statistical Manual of Mental Disorders III-R and IV criteria of functional limitation documented by an informant used in ADAMS effectively concentrated the diagnosis of dementia toward a relatively higher level of cognitive impairment. ADAMS separately identified a category of cognitive impairment not dementia and within that group there were a substantial number of cases with "prodromal" AD (a maximum of 1.95 million with upweighting). Second, a substantial proportion of dementia in ADAMS was attributed to either vascular disease (representing a maximum of 0.59 million with upweighting) or undetermined etiology (a maximum of 0.34 million), whereas most dementia, including mixed dementia, was attributed to AD in the Chicago Health and Aging Project.

CONCLUSION: The diagnosis of AD in population studies is a complex process. When a diagnosis of AD excludes persons meeting criteria for vascular dementia, when not all persons with dementia are assigned an etiology, and when a diagnosis of dementia requires an informant report of functional limitations, the prevalence is substantially lower and the diagnosed cases most likely have a relatively higher level of impairment.

}, keywords = {Aged, Aged, 80 and over, Alzheimer disease, Community Health Planning, Comorbidity, Dementia, Diagnosis, Differential, Female, Humans, Incidence, Male, Prevalence, United States}, issn = {1552-5279}, doi = {10.1016/j.jalz.2010.11.006}, author = {Robert S Wilson and David R Weir and Sue E Leurgans and Denis A Evans and Liesi Hebert and Kenneth M. Langa and Brenda L Plassman and Brent J. Small and David A Bennett} } @article {5917, title = {Updates to HRS Sample Weights}, year = {2011}, institution = {Institute for Social Research, University of Michigan}, address = {Ann Arbor, Michigan}, keywords = {Methodology}, author = {Mary Beth Ofstedal and David R Weir and Chen, K.T. and James Wagner} } @article {7452, title = {Clinical complexity in middle-aged and older adults with diabetes: the Health and Retirement Study.}, journal = {Med Care}, volume = {48}, year = {2010}, month = {2010 Apr}, pages = {327-34}, publisher = {48}, abstract = {

BACKGROUND: Some patients with diabetes may have health status characteristics that could make diabetes self-management (DSM) difficult and lead to inadequate glycemic control, or limit the benefit of some diabetes management interventions.

OBJECTIVE: To investigate how many older and middle-aged adults with diabetes have such health status characteristics.

DESIGN: Secondary data analysis of a nationally representative health interview survey, the Health and Retirement Study, and its diabetes mail-out survey.

SETTING/PARTICIPANTS: Americans aged 51 and older with diabetes (n = 3506 representing 13.6 million people); aged 56 and older in diabetes survey (n = 1132, representing 9.9 million).

MEASUREMENTS: Number of adults with diabetes and (a) relatively good health; (b) health status that could make DSM difficult (eg, comorbidities, impaired instrumental activities of daily living; and (c) characteristics like advanced dementia and activities of daily living dependency that could limit benefit of some diabetes management. Health and Retirement Study measures included demographics. Diabetes Survey included self-measured HbA1c.

RESULTS: Nearly 22\% of adults > or =51 with diabetes (about 3 million people) have health characteristics that could make DSM difficult. Another 10\% (1.4 million) may receive limited benefit from some diabetes management. Mail-out respondents with health characteristics that could make DSM difficult had significantly higher mean HbA1c compared with people with relatively good health (7.6\% vs. 7.3\%, P < 0.04.).

CONCLUSIONS: Some middle-aged as well as older adults with diabetes have health status characteristics that might make DSM difficult or of limited benefit. Current diabetes quality measures, including measures of glycemic control, may not reflect what is possible or optimal for all patient groups.

}, keywords = {Aged, Cross-Sectional Studies, Diabetes Complications, Diabetes Mellitus, Type 2, Female, Glycemic Index, Health Status, Health Surveys, Humans, Male, Middle Aged, Quality of Health Care, Self Care, Severity of Illness Index, Treatment Failure, United States}, issn = {1537-1948}, doi = {10.1097/mlr.0b013e3181ca4035}, author = {Caroline S Blaum and Christine T Cigolle and Cynthia Boyd and Jennifer L. Wolff and Zhiyi Tian and Kenneth M. Langa and David R Weir} } @article {5803, title = {Personality, Lifetime Earnings, and Retirement Wealth}, year = {2010}, institution = {Michigan Retirement Research Center, University of Michigan}, address = {Ann Arbor, MI}, abstract = {Studies of adolescents and young adults have shown that schooling impacts economic outcomes beyond its impact on cognitive ability. Research has also shown that the personality trait of conscientiousness predicts health outcomes, academic outcomes, and divorce. Using the Big Five taxonomy of personality traits, this study examines whether non-cognitive traits are related to economic success over the life course. Examining Health and Retirement Study survey data linked to Social Security records on over 10,000 adults age 50 and over, we investigate the relationship of personality traits to economic outcomes. Controlling for cognitive ability and background variables, do more conscientious and emotionally stable adults have higher lifetime earnings, and is this due to higher annual earnings, longer work lives, or both? Do more conscientious adults save a higher proportion of their earnings for retirement, and does conscientiousness of each partner in a married couple matter? Do conscientiousness and emotional stability interact such that the effects of conscientiousness are greater among less emotionally stable adults?}, keywords = {Health Conditions and Status, Healthcare, Public Policy, Social Security}, url = {https://ideas.repec.org/p/mrr/papers/wp235.html}, author = {Angela Lee Duckworth and David R Weir and Michigan Retirement Research Center} } @article {7540, title = {Recent developments in longitudinal studies of aging in the United States.}, journal = {Demography}, volume = {47 Suppl}, year = {2010}, note = {Hauser, Robert M Weir, David AG-21079/AG/NIA NIH HHS/United States AG-9775/AG/NIA NIH HHS/United States U01 AG009740/AG/NIA NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov{\textquoteright}t United States Demography Demography. 2010;47 Suppl:S111-30.}, month = {2010}, pages = {S111-30}, publisher = {47 Suppl}, abstract = {

We review recent developments in longitudinal studies of aging, focusing on the Wisconsin Longitudinal Study (WLS) and the Health and Retirement Study (HRS). Both studies are part of a trend toward biosocial surveys in which biological measurement is joined with traditional survey techniques, and a related trend toward greater harmonization across studies. Both studies have collected DNA samples and are working toward genotyping that would allow broadly based association studies. Increased attention to psychological measurement of personality and of cognitive ability using adaptive testing structures has also been shared across the studies. The HRS has expanded its economic measurement to longitudinal studies of consumption and to broader-based measurement of pension and Social Security wealth. It has added biomarkers of cardiovascular risk. The WLS has developed an integrated approach to the study of death and bereavement and an innovative use of high school yearbook photographs to capture information about health in early life of its participants.

}, keywords = {Aging, Data collection, Demography, Genome-Wide Association Study, Health Status Indicators, Health Surveys, Humans, Longitudinal Studies, Research Design, Socioeconomic factors, United States}, issn = {0070-3370}, doi = {10.1353/dem.2010.0012}, author = {Hauser, Robert M. and David R Weir} } @article {5829, title = {Socio-economic Status and Mortality: Perceptions and Outcomes}, year = {2010}, abstract = {This paper draws on over 300,000 person-years of mortality observation on over 30,000 participants in the Health and Retirement Study (HRS) to study the relationship of education, income, and wealth to mortality expectations and mortality outcomes in older Americans. Using quintiles to facilitate comparison across variables, we find that all three SES measures significantly predict mortality, but that in joint models education is dominated by the other two which are realized later in life, and particularly by wealth. As others have found, SES differentials in mortality decline with age, though wealth remains a powerful determinant even at advanced ages. When strictly interpreted as expressions of relative risk, the subjective probabilities of survival offered by HRS respondents substantially understate the true differentials by SES, as they do for other factors like smoking and very low or very high body weight. In particular, the large mortality disadvantage of low wealth is not recognized. SES accounts for most of black-white differentials in mortality, whereas it unveils an Hispanic advantage relative to other whites that was masked by lower SES.}, keywords = {Demographics, Health Conditions and Status}, url = {https://paa2010.princeton.edu/papers/101560}, author = {David R Weir} } @article {7495, title = {Take-up of Medicare Part D: results from the Health and Retirement Study.}, journal = {J Gerontol B Psychol Sci Soc Sci}, volume = {65}, year = {2010}, note = {Times Cited: 6}, month = {2010 Jul}, pages = {492-501}, publisher = {65}, abstract = {

OBJECTIVES: To estimate the impact of Medicare Part D on prescription drug coverage among elderly Medicare beneficiaries and to analyze the predictors of program enrollment ("take-up") among those with no prior drug coverage.

METHODS: Multivariate analyses of data from the 2002, 2004, and 2006 waves of the Health and Retirement Study.

RESULTS: Take-up of Part D among those without drug coverage in 2004 was high; about 50\%-60\% of this group had Part D coverage in 2006. Only 7\% of senior citizens lacked drug coverage in 2006 compared with 24\% in 2004. Demand for prescription drugs was the most important determinant of the decision to enroll in Part D among those with no prior coverage. Many of those who remained without coverage in 2006 reported that they do not use prescribed medicines, and the majority had relatively low out-of-pocket spending.

CONCLUSION: For the most part, Medicare beneficiaries seem to have been able to make economically rational decisions about Part D enrollment despite the complexity of the program.

}, keywords = {Aged, ethnicity, Humans, Longitudinal Studies, Medically Uninsured, Medicare Part D, Multivariate Analysis, Poverty, prescription drugs, Prescription Fees, United States}, issn = {1758-5368}, doi = {10.1093/geronb/gbp107}, author = {Helen G Levy and David R Weir} } @article {5811, title = {Validating Diabetes Disease Status in Claims and Survey Data. Proceedings of the 2010 International Methodology Symposium: The Interplay among Censuses, Surveys and Administrative Data}, year = {2010}, institution = {Ottawa}, keywords = {Health Conditions and Status, Methodology}, author = {Joseph W Sakshaug and David R Weir and Lauren Hersch Nicholas} } @article {7403, title = {The accuracy of Medicare claims as an epidemiological tool: the case of dementia revisited.}, journal = {J Alzheimers Dis}, volume = {17}, year = {2009}, month = {2009}, pages = {807-15}, publisher = {17}, abstract = {

Our study estimates the sensitivity and specificity of Medicare claims to identify clinically-diagnosed dementia, and documents how errors in dementia assessment affect dementia cost estimates. We compared Medicare claims from 1993-2005 to clinical dementia assessments carried out in 2001-2003 for the Aging Demographics and Memory Study (ADAMS) cohort (n = 758) of the Health and Retirement Study. The sensitivity and specificity of Medicare claims was 0.85 and 0.89 for dementia (0.64 and 0.95 for AD). Persons with dementia cost the Medicare program (in 2003) $7,135 more than controls (P < 0.001) when using claims to identify dementia, compared to $5,684 more when using ADAMS (P < 0.001). Using Medicare claims to identify dementia results in a 110\% increase in costs for those with dementia as compared to a 68\% increase when using ADAMS to identify disease, net of other variables. Persons with false positive Medicare claims notations of dementia were the most expensive group of subjects ($11,294 versus $4,065, for true negatives P < 0.001). Medicare claims overcount the true prevalence of dementia, but there are both false positive and negative assessments of disease. The use of Medicare claims to identify dementia results in an overstatement of the increase in Medicare costs that are due to dementia.

}, keywords = {Aged, Aged, 80 and over, Alzheimer disease, Cohort Studies, Dementia, Female, Health Care Costs, Humans, Insurance Claim Reporting, Male, Medicare, Prevalence, Sensitivity and Specificity, United States}, issn = {1875-8908}, doi = {10.3233/JAD-2009-1099}, author = {Donald H. Taylor Jr. and {\O}stbye, Truls and Kenneth M. Langa and David R Weir and Brenda L Plassman} } @article {5761, title = {Aging, Demographics and Memory Study (ADAMS): Sample Design, Weighting and Analysis for ADAMS}, year = {2009}, institution = {Institute for Social Research, University of Michigan}, address = {Ann Arbor, Michigan}, abstract = {This technical report describes the sample design, design-based weighting and analysis procedures for the Aging, Demographics and Memory Study (ADAMS), a national study that recruited Health and Retirement Study (HRS) panel members to undergo a psychometric evaluation and clinical assessment visit. Langa et al. (2005) describe the general design and methods for the ADAMS including relevant background on the HRS longitudinal sample. This document provides additional detail on the sample design for the ADAMS including a description of survey sample selection, sample attrition and nonresponse, population weights, design-based variance estimation and related topics of importance to analysts of the ADAMS data.}, keywords = {Health Conditions and Status, Methodology}, author = {Steven G Heeringa and Gwenith G Fisher and Michael D Hurd and Kenneth M. Langa and Mary Beth Ofstedal and Brenda L Plassman and Rogers, Willard and David R Weir} } @article {7346, title = {Cognitive health among older adults in the United States and in England.}, journal = {BMC Geriatr}, volume = {9}, year = {2009}, note = {PMID: 19555494}, month = {2009 Jun 25}, pages = {23}, publisher = {9}, abstract = {

BACKGROUND: Cognitive function is a key determinant of independence and quality of life among older adults. Compared to adults in England, US adults have a greater prevalence of cardiovascular risk factors and disease that may lead to poorer cognitive function. We compared cognitive performance of older adults in the US and England, and sought to identify sociodemographic and medical factors associated with differences in cognitive function between the two countries.

METHODS: Data were from the 2002 waves of the US Health and Retirement Study (HRS) (n = 8,299) and the English Longitudinal Study of Ageing (ELSA) (n = 5,276), nationally representative population-based studies designed to facilitate direct comparisons of health, wealth, and well-being. There were differences in the administration of the HRS and ELSA surveys, including use of both telephone and in-person administration of the HRS compared to only in-person administration of the ELSA, and a significantly higher response rate for the HRS (87\% for the HRS vs. 67\% for the ELSA). In each country, we assessed cognitive performance in non-hispanic whites aged 65 and over using the same tests of memory and orientation (0 to 24 point scale).

RESULTS: US adults scored significantly better than English adults on the 24-point cognitive scale (unadjusted mean: 12.8 vs. 11.4, P < .001; age- and sex-adjusted: 13.2 vs. 11.7, P < .001). The US cognitive advantage was apparent even though US adults had a significantly higher prevalence of cardiovascular risk factors and disease. In a series of OLS regression analyses that controlled for a range of sociodemographic and medical factors, higher levels of education and wealth, and lower levels of depressive symptoms, accounted for some of the US cognitive advantage. US adults were also more likely to be taking medications for hypertension, and hypertension treatment was associated with significantly better cognitive function in the US, but not in England (P = .014 for treatment x country interaction).

CONCLUSION: Despite methodological differences in the administration of the surveys in the two countries, US adults aged >/= 65 appeared to be cognitively healthier than English adults, even though they had a higher burden of cardiovascular risk factors and disease. Given the growing number of older adults worldwide, future cross-national studies aimed at identifying the medical and social factors that might prevent or delay cognitive decline in older adults would make important and valuable contributions to public health.

}, keywords = {Aged, Aged, 80 and over, Aging, Cognition, Cognition Disorders, Cohort Studies, Cross-Sectional Studies, England, Female, Health Status, Humans, Longitudinal Studies, Male, Neuropsychological tests, United States}, issn = {1471-2318}, doi = {10.1186/1471-2318-9-23}, author = {Kenneth M. Langa and David J Llewellyn and Iain A Lang and David R Weir and Robert B Wallace and Mohammed U Kabeto and Felicia A Huppert} } @article {5780, title = {Cross-Wave Prospective Social Security Wealth Measures of Pre-Retirees, Public Release: Data Description and Usage}, year = {2009}, institution = {Institute for Social Research, University of Michigan}, address = {Ann Arbor, Michigan}, abstract = {The Prospective Social Security Wealth Measures of Pre-Retirees data set consists of respondent-level, cross-sectional files constructed from the employment sections of the HRS 1992 (wave 1), HRS 1998 (wave 4), HRS 2004 (wave 7) and the restricted SSA summary and detailed earnings and benefits files. In this public use file, we calculate wealth only for individuals who have not yet retired (as evidenced by claiming SS benefits) (see Section III.C). Each individual is uniquely identified by the concatenation of the household ID and the person number, HHID and PN. We organize the data to match the organization of the RAND HRS data files.}, keywords = {Net Worth and Assets, Social Security}, author = {Kandice Kapinos and Charles Brown and Michael A. Nolte and Helena Stolyarova and David R Weir} } @article {5739, title = {Take-Up of Medicare Part D and the SSA Subsidy: Early Results from the Health and Retirement Study}, year = {2009}, note = {http://www.nber.org/papers/w14692}, institution = {Cambridge, MA, National Bureau of Economic Research, Working Paper 14692}, abstract = {We analyze newly available data from the Health and Retirement Study on senior citizens take-up of Medicare Part D and the associated SSA Low-Income Subsidy. We find that economic factors specifically, demand for prescription drugs - drove the decision to enroll in Part D. For the most part, individuals with employer-sponsored coverage in 2004 kept that coverage, as they should have. Individuals with no prescription drug coverage in 2004 mostly enrolled in Part D or obtained other coverage; many of those who remained without coverage reported that they do not use prescribed medicines. Take-up of the SSA Extra Help subsidy seems to have been more problematic, with many Part D beneficiaries unaware of the subsidy program or unsure about their eligibility. There is apparent under-reporting in the HRS of participation in the subsidy program, suggesting that some who profess to be unaware of the program may actually be participating in it. In terms of respondents subjective experiences of decision-making, the majority report having had little or no difficulty with the Part D enrollment decision and being confident that they made the right decision. Thus, for the most part, despite the complexity of the program, Medicare beneficiaries seem to have been able to make economically rational decisions in which they had confidence, although additional intervention for low-income beneficiaries may be desirable.}, keywords = {Healthcare, Medicare/Medicaid/Health Insurance}, url = {http://www.nber.org/papers/w14692}, author = {Helen G Levy and David R Weir} } @article {5736, title = {Documentation of Health Behaviors and Risk Factors Measured in the Health and Retirement Study (HRS/AHEAD)}, year = {2008}, institution = {Institute for Social Research, University of Michigan}, address = {Ann Arbor, Michigan}, abstract = {The two most important negative behaviors for population health are smoking, which is declining over time, and obesity, which is on the rise. Recognizing the important role of health behaviors and risk factors with respect to issues of key importance to the HRS (health, employment, wealth, timing of retirement), the original designers of the HRS incorporated a set of core measures of health behaviors at the outset. These measures have been expanded over time. The health behaviors and risk factors that are covered in the HRS include: Cigarette smoking (current and past behavior); Alcohol consumption (current behavior and past drinking problems); Body mass index (derived from self-reports of height and weight); Exercise (current level); Preventive health screenings. This report is organized as follows. Section II provides an inventory of the measures of health behaviors and risk factors that are covered in HRS, noting additions and changes that have occurred across waves. Special methodological issues that must be considered when using these data are covered in Section III. Section IV (and corresponding Tables 2-28) presents prevalence estimates and frequency counts for each of the health behavior and risk factor measures over time. Lastly, Section V addresses data quality by comparing HRS prevalence estimates with those from other surveys, reviewing results from some of the studies that have used HRS data to study health behaviors and risk factors, and investigating the level of missing data for these measures.}, keywords = {Health Conditions and Status, Methodology}, author = {Kristi Rahrig Jenkins and Mary Beth Ofstedal and David R Weir} } @article {5734, title = {Documentation of Physical Measures, Anthropometrics and Blood Pressure in the Health and Retirement Study}, year = {2008}, institution = {Institute for Social Research, University of Michigan}, address = {Ann Arbor, Michigan}, abstract = {The assessment of physical performance is an important component of the evaluation of functioning of older persons. The HRS has employed a set of standardized assessments of lung function, grip strength, balance, and walking speed. In addition, HRS collected measures of blood pressure, height, weight, and waist circumference. In 2006, HRS included the following measurements, administered in this order: Blood pressure; Lung function; Hand grip strength; Balance tests; Timed walk; Height; Weight; Waist circumference. This report describes the following for each of the measures listed above: Rationale and key citations; Sample description; Measure description; Equipment; Protocol description; Special instructions}, keywords = {Health Conditions and Status, Healthcare, Methodology}, author = {Eileen M. Crimmins and Heidi M Guyer and Kenneth M. Langa and Mary Beth Ofstedal and Robert B Wallace and David R Weir} } @article {5723, title = {Guide to Content of the HRS Psychosocial Leave-Behind Participant Lifestyle Questionnaires: 2004 and 2006}, year = {2008}, institution = {Ann Arbor, The University of Michigan}, abstract = {In 2004, HRS added a new feature for data collection in the form of self-administered questionnaires that were left with respondents upon the completion of an in-person Core Interview. These are referred to as Leave-Behind Questionnaires and electronic versions of the questionnaires are included in the 2004 Final release and 2006 Early Release. The purpose of the Leave-Behind Questionnaire is to collect additional information from respondents without adding to the interview length. Two separate questionnaires on different topics were included in HRS 2004: a) Participant Lifestyle Questionnaire, which measures psychosocial issues that are described in much more detail later in this report, and b) Participant questionnaire on Work and Health, which included a series of disability vignettes in which people with various levels of physical and mental health impairment were described and respondents were asked to indicate the extent to which they think the person described is limited in the kind or amount of work they can do. At the beginning of the vignettes, respondents were asked to rate their own degree of limitation in the kind or amount of work they can do.}, keywords = {Disabilities, Health Conditions and Status}, url = {http://hrsonline.isr.umich.edu/sitedocs/userg/HRS2006LBQscale.pdf}, author = {Philippa J Clarke and Gwenith G Fisher and House, Jim and Jacqui Smith and David R Weir} } @article {7201, title = {Prevalence of cognitive impairment without dementia in the United States.}, journal = {Ann Intern Med}, volume = {148}, year = {2008}, month = {2008 Mar 18}, pages = {427-34}, publisher = {148}, abstract = {

BACKGROUND: Cognitive impairment without dementia is associated with increased risk for disability, increased health care costs, and progression to dementia. There are no population-based prevalence estimates of this condition in the United States.

OBJECTIVE: To estimate the prevalence of cognitive impairment without dementia in the United States and determine longitudinal cognitive and mortality outcomes.

DESIGN: Longitudinal study from July 2001 to March 2005.

SETTING: In-home assessment for cognitive impairment.

PARTICIPANTS: Participants in ADAMS (Aging, Demographics, and Memory Study) who were age 71 years or older drawn from the nationally representative HRS (Health and Retirement Study). Of 1770 selected individuals, 856 completed initial assessment, and of 241 selected individuals, 180 completed 16- to 18-month follow-up assessment.

MEASUREMENTS: Assessments, including neuropsychological testing, neurologic examination, and clinical and medical history, were used to assign a diagnosis of normal cognition, cognitive impairment without dementia, or dementia. National prevalence rates were estimated by using a population-weighted sample.

RESULTS: In 2002, an estimated 5.4 million people (22.2\%) in the United States age 71 years or older had cognitive impairment without dementia. Prominent subtypes included prodromal Alzheimer disease (8.2\%) and cerebrovascular disease (5.7\%). Among participants who completed follow-up assessments, 11.7\% with cognitive impairment without dementia progressed to dementia annually, whereas those with subtypes of prodromal Alzheimer disease and stroke progressed at annual rates of 17\% to 20\%. The annual death rate was 8\% among those with cognitive impairment without dementia and almost 15\% among those with cognitive impairment due to medical conditions.

LIMITATIONS: Only 56\% of the nondeceased target sample completed the initial assessment. Population sampling weights were derived to adjust for at least some of the potential bias due to nonresponse and attrition.

CONCLUSION: Cognitive impairment without dementia is more prevalent in the United States than dementia, and its subtypes vary in prevalence and outcomes.

}, keywords = {Aged, Aged, 80 and over, Cognition Disorders, Dementia, disease progression, Humans, Longitudinal Studies, Prevalence, United States}, issn = {1539-3704}, doi = {10.7326/0003-4819-148-6-200803180-00005}, author = {Brenda L Plassman and Kenneth M. Langa and Gwenith G Fisher and Steven G Heeringa and David R Weir and Mary Beth Ofstedal and James R Burke and Michael D Hurd and Guy G Potter and Willard L Rodgers and David C Steffens and John J McArdle and Robert J. Willis and Robert B Wallace} } @article {7290, title = {Racial and Ethnic Differences in Undiagnosed and Poorly Managed Diabetes and Hypertension: Combining Population Surveys with Biomarker Data (HRS2006).}, journal = {The Gerontologist}, volume = {48}, year = {2008}, pages = {1}, publisher = {48}, abstract = {CA Diabetes and hypertension are common conditions of aging that increase risk for cardiovascular events if not properly treated.Concerns about undiagnosed, and inadequately treated disease, are particularly strong for minority populations.Diabetes diagnosis rates vary from 16 among whites to 29 for blacks and 27 for Hispanics.}, keywords = {Demographics, Health Conditions and Status}, author = {David R Weir and Eileen M. Crimmins} } @inbook {5211, title = {Are Baby Boomers Living Well Longer?}, booktitle = {Redefining Retirement: How Will Boomers Fare?}, year = {2007}, note = {ProCite field 6 : In ProCite field 8 : eds}, publisher = {Oxford University Press}, organization = {Oxford University Press}, address = {New York, NY}, abstract = {This chapter uses the Health and Retirement Study to describe the relationship between work and health for older persons by age. We examine not only the patterns within a given cross-section, but also we study trends in health at ages 51-56 between 1992 and 2004. Most retirement occurs well before the onset of work-limiting disability, leaving a large reserve of potential for longer worklives. Baby Boomers will likely have to draw on this reserve, yet its health is not demonstrably better than that of persons born a dozen years earlier. Nevertheless, advances in medical care for health conditions that most 51-56 year olds have not yet encountered may still yield better health at older ages for the Boomer cohort.}, keywords = {Expectations, Health Conditions and Status, Other}, url = {https://repository.upenn.edu/prc_papers/364/}, author = {David R Weir} } @article {7173, title = {Beyond comorbidity counts: how do comorbidity type and severity influence diabetes patients{\textquoteright} treatment priorities and self-management?}, journal = {J Gen Intern Med}, volume = {22}, year = {2007}, month = {2007 Dec}, pages = {1635-40}, publisher = {22}, abstract = {

BACKGROUND: The majority of older adults have 2 or more chronic conditions and among patients with diabetes, 40\% have at least three.

OBJECTIVE: We sought to understand how the number, type, and severity of comorbidities influence diabetes patients{\textquoteright} self-management and treatment priorities.

DESIGN: Cross-sectional observation study.

PATIENTS: A total of 1,901 diabetes patients who responded to the 2003 Health and Retirement Study (HRS) diabetes survey.

MEASUREMENTS: We constructed multivariate models to assess the association between presence of comorbidities and each of 2 self-reported outcomes, diabetes prioritization and self-management ability, controlling for patient demographics. Comorbidity was characterized first by a count of all comorbid conditions, then by the presence of specific comorbidity subtypes (microvascular, macrovascular, and non-diabetes related), and finally by severity of 1 serious comorbidity: heart failure (HF).

RESULTS: 40\% of respondents had at least 1 microvascular comorbidity, 79\% at least 1 macrovascular comorbidity, and 61\% at least 1 non-diabetes-related comorbidity. Patients with a greater overall number of comorbidities placed lower priority on diabetes and had worse diabetes self-management ability scores. However, only macrovascular and non-diabetes-related comorbidities, but not microvascular comorbidities, were associated with lower diabetes prioritization, whereas higher numbers of microvascular, macrovascular, and non-diabetes-related conditions were all associated with lower diabetes self-management ability scores. Severe, but not mild, HF was associated with lower diabetes prioritization and self-management scores.

CONCLUSIONS: The type and severity of comorbid conditions, and not just the comorbidity count, influence diabetes patients{\textquoteright} self-management. Patients with severely symptomatic comorbidities and those with conditions they consider to be unrelated to diabetes may need additional support in making decisions about care priorities and self-management activities.

}, keywords = {Aged, Attitude to Health, Cohort Studies, Comorbidity, Cross-Sectional Studies, Diabetes Mellitus, Female, Health Priorities, Heart Failure, Humans, Male, Middle Aged, Self Care, Severity of Illness Index, United States}, issn = {1525-1497}, doi = {10.1007/s11606-007-0313-2}, author = {Eve A Kerr and Michele M Heisler and Sarah L. Krein and Mohammed U Kabeto and Kenneth M. Langa and David R Weir and John D Piette} } @article {7150, title = {Do panel surveys really make people sick? A commentary on Wilson and Howell (60:11, 2005, 2623-2627).}, journal = {Soc Sci Med}, volume = {65}, year = {2007}, month = {2007 Sep}, pages = {1071-7; discussion 1078-81}, publisher = {65}, abstract = {

In a recent article in this journal, Wilson and Howell [2005. Do panel surveys make people sick? US arthritis trends in the Health and Retirement Survey. Social Science \& Medicine, 60(11), 2623-2627.] argue that the sharp trend of rising age-specific arthritis prevalence from 1992 to 2000 in the USA among those in their 50s based on the original Health and Retirement Study (HRS) cohort of respondents is "almost surely spurious." Their reasons are that no such trend is found in the National Health Interview Study (NHIS) over this same time period, and that an introduction of a new birth cohort into HRS in 1998 also indicates no trend. They also claim that there may be an inherent bias in panel surveys leading respondents to report greater levels of disease as the duration of their participation in the panel increases. This bias, which they call "panel conditioning," suggests a tendency for participants in a longitudinal survey to seek out medical care and diagnosis of symptoms asked about in previous waves. In this paper, we show that the evidence presented and the conclusions reached by Wilson and Howell are incorrect. Properly analyzed, three national health surveys--the NHIS, National Health and Nutrition Examination Survey (NHANES), and HRS--all show increases in age-specific arthritis prevalence during the 1990s. Since the new HRS sample cohort introduced in 1998 represents only a part of that birth cohort, we also demonstrate that Wilson and Howell{\textquoteright}s evidence in favor of panel conditioning was flawed. We find little indication of panel conditioning among existing participants in a panel survey.

}, keywords = {Arthritis, Female, Health Surveys, Humans, Male, Middle Aged, Prevalence, United States}, issn = {0277-9536}, doi = {10.1016/j.socscimed.2007.04.019}, author = {David R Weir and James P Smith} } @article {7178, title = {Does physician communication influence older patients{\textquoteright} diabetes self-management and glycemic control? Results from the Health and Retirement Study (HRS).}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {62}, year = {2007}, month = {2007 Dec}, pages = {1435-42}, publisher = {62A}, abstract = {

BACKGROUND: Effective chronic disease self-management among older adults is crucial for improved clinical outcomes. We assessed the relative importance of two dimensions of physician communication-provision of information (PCOM) and participatory decision-making (PDM)-for older patients{\textquoteright} diabetes self-management and glycemic control.

METHODS: We conducted a national cross-sectional survey among 1588 older community-dwelling adults with diabetes (response rate: 81\%). Independent associations were examined between patients{\textquoteright} ratings of their physician{\textquoteright}s PCOM and PDM with patients{\textquoteright} reported diabetes self-management (medication adherence, diet, exercise, blood glucose monitoring, and foot care), adjusting for patient sociodemographics, illness severity, and comorbidities. Among respondents for whom hemoglobin A1c (HbA1c) values were available (n=1233), the relationship was assessed between patient self-management and HbA1c values.

RESULTS: In separate multivariate regressions, PCOM and PDM were each associated with overall diabetes self-management (p<.001) and with all self-management domains (p<.001 in all models), with the exception of PDM not being associated with medication adherence. In models with both PCOM and PDM, PCOM alone predicted medication adherence (p=.001) and foot care (p=.002). PDM alone was associated with exercise and blood glucose monitoring (both p<.001) and was a stronger independent predictor than PCOM of diet. Better patient ratings of their diabetes self-management were associated with lower HbA1c values (B= -.10, p=.005).

CONCLUSION: Among these older adults, both their diabetes providers{\textquoteright} provision of information and efforts to actively involve them in treatment decision-making were associated with better overall diabetes self-management. Involving older patients in setting chronic disease goals and decision-making, however, appears to be especially important for self-care areas that demand more behaviorally complex lifestyle adjustments such as exercise, diet, and blood glucose monitoring.

}, keywords = {Aged, Blood Glucose, Communication, Cross-Sectional Studies, Diabetes Mellitus, Female, Glycated Hemoglobin, Humans, Male, Multivariate Analysis, Physician-Patient Relations, Self Care}, issn = {1079-5006}, doi = {10.1093/gerona/62.12.1435}, author = {Michele M Heisler and Cole, Ian and David R Weir and Eve A Kerr and Rodney A. Hayward} } @inbook {5219, title = {Elastic Powers: The Integration of Biomarkers into the Health and Retirement Study}, booktitle = {Bio-Social Surveys: Current insight and future promise}, year = {2007}, note = {ProCite field 6 : In ProCite field 8 : eds}, pages = {78-95}, publisher = {The National Academies Press}, organization = {The National Academies Press}, address = {Washington, DC}, keywords = {Methodology}, url = {https://www.ncbi.nlm.nih.gov/books/NBK62437/}, author = {David R Weir}, editor = {Weinstein, Maxine and James W Vaupel and Kenneth W. Wachter} } @article {7168, title = {Mechanisms for racial and ethnic disparities in glycemic control in middle-aged and older Americans in the health and retirement study.}, journal = {Arch Intern Med}, volume = {167}, year = {2007}, month = {2007 Sep 24}, pages = {1853-60}, publisher = {167}, abstract = {

BACKGROUND: Mechanisms for racial/ethnic disparities in glycemic control are poorly understood.

METHODS: A nationally representative sample of 1901 respondents 55 years or older with diabetes mellitus completed a mailed survey in 2003; 1233 respondents completed valid at-home hemoglobin A(1c) (HbA(1c)) kits. We constructed multivariate regression models with survey weights to examine racial/ethnic differences in HbA(1c) control and to explore the association of HbA(1c) level with sociodemographic and clinical factors, access to and quality of diabetes health care, and self-management behaviors and attitudes.

RESULTS: There were no significant racial/ethnic differences in HbA(1c) levels in respondents not taking antihyperglycemic medications. In 1034 respondents taking medications, the mean HbA(1c) value (expressed as percentage of total hemoglobin) was 8.07\% in black respondents and 8.14\% in Latino respondents compared with 7.22\% in white respondents (P < .001). Black respondents had worse medication adherence than white respondents, and Latino respondents had more diabetes-specific emotional distress (P < .001). Adjusting for hypothesized mechanisms accounted for 14.0\% of the higher HbA(1c) levels in black respondents and 19.0\% in Latinos, with the full model explaining 22.0\% of the variance. Besides black and Latino ethnicity, only insulin use (P < .001), age younger than 65 years (P = .007), longer diabetes duration (P = .004), and lower self-reported medication adherence (P = .04) were independently associated with higher HbA(1c) levels.

CONCLUSIONS: Latino and African American respondents had worse glycemic control than white respondents. Socioeconomic, clinical, health care, and self-management measures explained approximately a fifth of the HbA(1c) differences. One potentially modifiable factor for which there were racial disparities--medication adherence--was among the most significant independent predictors of glycemic control.

}, keywords = {Aged, Aged, 80 and over, Black People, Diabetes Mellitus, Female, Glycated Hemoglobin, Health Services Accessibility, Hispanic or Latino, Humans, Longitudinal Studies, Male, Middle Aged, Patient Compliance, Socioeconomic factors, Treatment Refusal, United States, White People}, issn = {0003-9926}, doi = {10.1001/archinte.167.17.1853}, author = {Michele M Heisler and Jessica Faul and Rodney A. Hayward and Kenneth M. Langa and Caroline S Blaum and David R Weir} } @article {7164, title = {Prevalence of dementia in the United States: the aging, demographics, and memory study.}, journal = {Neuroepidemiology}, volume = {29}, year = {2007}, month = {2007}, pages = {125-32}, publisher = {29}, abstract = {

AIM: To estimate the prevalence of Alzheimer{\textquoteright}s disease (AD) and other dementias in the USA using a nationally representative sample.

METHODS: The Aging, Demographics, and Memory Study sample was composed of 856 individuals aged 71 years and older from the nationally representative Health and Retirement Study (HRS) who were evaluated for dementia using a comprehensive in-home assessment. An expert consensus panel used this information to assign a diagnosis of normal cognition, cognitive impairment but not demented, or dementia (and dementia subtype). Using sampling weights derived from the HRS, we estimated the national prevalence of dementia, AD and vascular dementia by age and gender.

RESULTS: The prevalence of dementia among individuals aged 71 and older was 13.9\%, comprising about 3.4 million individuals in the USA in 2002. The corresponding values for AD were 9.7\% and 2.4 million individuals. Dementia prevalence increased with age, from 5.0\% of those aged 71-79 years to 37.4\% of those aged 90 and older.

CONCLUSIONS: Dementia prevalence estimates from this first nationally representative population-based study of dementia in the USA to include subjects from all regions of the country can provide essential information for effective planning for the impending healthcare needs of the large and increasing number of individuals at risk for dementia as our population ages.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Cohort Studies, Dementia, Female, Geriatric Assessment, Health Surveys, Humans, Logistic Models, Male, Prevalence, Sex Distribution, United States}, issn = {1423-0208}, doi = {10.1159/000109998}, author = {Brenda L Plassman and Kenneth M. Langa and Gwenith G Fisher and Steven G Heeringa and David R Weir and Mary Beth Ofstedal and James R Burke and Michael D Hurd and Guy G Potter and Willard L Rodgers and David C Steffens and Robert J. Willis and Robert B Wallace} } @article {7002, title = {The Aging, Demographics and Memory Study: Study Design and Methods}, journal = {Neuroepidemiology}, volume = {25}, year = {2005}, pages = {181-191}, publisher = {25}, abstract = {Objective: We describe the design and methods of the Aging, Demographics, and Memory Study (ADAMS), a new national study that will provide data on the antecedents, prevalence, outcomes, and costs of dementia and cognitive impairment, not demented (CIND) using a unique study design based on the nationally representative Health and Retirement Study (HRS). We also illustrate potential uses of the ADAMS data and provide information to interested researchers on obtaining ADAMS and HRS data. Methods: The ADAMS is the first population-based study of dementia in the United States to include subjects from all regions of the country, while at the same time using a single standardized diagnostic protocol in a community-based sample. A sample of 856 individuals aged 70 or older who were participants in the on-going HRS received an extensive in-home clinical and neuropsychological assessment to determine a diagnosis of normal, CIND, or dementia. Within the CIND and dementia categories, subcategories (e.g., Alzheimer disease, vascular dementia) were assigned to denote the etiology of cognitive impairment. Conclusion: Linking the ADAMS dementia clinical assessment data to the wealth of available longitudinal HRS data on health, health care utilization, informal care, and economic resources and behavior, will provide a unique opportunity to study the onset of CIND and dementia in a nationally-representative population-based sample, as well as the risk factors, prevalence, outcomes, and costs of CIND and dementia.}, keywords = {Health Conditions and Status, Healthcare}, author = {Kenneth M. Langa and Brenda L Plassman and Robert B Wallace and A. Regula Herzog and Steven G Heeringa and Mary Beth Ofstedal and James F. Burke and Gwenith G Fisher and Fultz, Nancy H. and Michael D Hurd and Guy G Potter and Willard L Rodgers and David C Steffens and David R Weir} } @article {5619, title = {Documentation of Chronic Disease Measures in the Health and Retirement Study}, year = {2005}, institution = {Institute for Social Research, University of Michigan}, address = {Ann Arbor, Michigan}, abstract = {The focus of this report is on (1) self-rated overall health status and recent changes in overall health, (2) the presence of common chronic medical conditions and follow-up questions concerning treatments in all waves of the core HRS/AHEAD through 2002.}, keywords = {Health Conditions and Status, Healthcare, Methodology}, author = {Gwenith G Fisher and Jessica Faul and David R Weir and Robert B Wallace} } @article {5643, title = {HRS 2001 HUMS College Tuition Imputations}, year = {2005}, institution = {Institute for Social Research, University of Michigan}, address = {Ann Arbor, Michigan}, abstract = {HRS 2001 Off-Year Mail Survey on Human Capital Investment (HRS 2001 HUMS) collected important information on the education of HRS respondents children. Among other things, the survey asked a selected set of HRS respondents to provide information about whether a child attended a two- or four-year undergraduate college, the total number of years in college(s), his or her age when he or she last attended college, and the name of the college that he or she last attended. One way to use the information is to produce college tuition data associated with each child, which can then be linked in an integrated analysis of family transfer with other family transfer information collected in the HRS core survey. In this document we describe what we have done in imputing HRS 2001 HUMS college tuitions. The general idea is to link the children college attendance information in HRS 2001 HUMS with a college tuition database (CASPAR) created and administered by the National Science Foundation. For 2000 and 2001, college cost data are also taken from the NCES IPEDS online database.}, keywords = {Consumption and Savings, Methodology, Net Worth and Assets}, author = {Cao, Honggao and John C Henretta and Norgard, T.M. and Beth J Soldo and David R Weir} } @article {7027, title = {Use of complementary medicine in older Americans: results from the Health and Retirement Study.}, journal = {Gerontologist}, volume = {45}, year = {2005}, month = {2005 Aug}, pages = {516-24}, publisher = {45}, abstract = {

PURPOSE: The correlates of complementary and alternative medicine (CAM) utilization among elders have not been fully investigated. This study was designed to identify such correlates in a large sample of older adults, thus generating new data relevant to consumer education, medical training, and health practice and policy.

DESIGN AND METHODS: A subsample from the 2000 Wave of the Health and Retirement Study (n = 1,099) aged 52 or older were surveyed regarding use of CAM (chiropractic, alternative practitioners, dietary and herbal supplements, and personal practices).

RESULTS: Of respondents over 65 years of age, 88\% used CAM, with dietary supplements and chiropractic most commonly reported (65\% and 46\%, respectively). Users of alternate practitioners and dietary supplements reported having more out-of-pocket expenses on health than nonusers of these modalities. Age correlated positively with use of dietary supplements and personal practices and inversely with alternative practitioner use. Men reported less CAM use than women, except for chiropractic and personal practices. Blacks and Hispanics used fewer dietary supplements and less chiropractic, but they reported more personal practices than Whites. Advanced education correlated with fewer chiropractic visits and more dietary and herbal supplement and personal practices use. Higher income, functional impairment, alcohol use, and frequent physician visits correlated with more alternative practitioner use. There was no association between CAM and number of chronic diseases.

IMPLICATIONS: The magnitude and patterns of CAM use among elders lend considerable importance to this field in public health policy making and suggest a need for further epidemiological research and ongoing awareness efforts for both patients and providers.

}, keywords = {Activities of Daily Living, Aged, Chi-Square Distribution, Complementary Therapies, Female, Humans, Male, Middle Aged, Regression Analysis, Surveys and Questionnaires, United States}, issn = {0016-9013}, doi = {10.1093/geront/45.4.516}, author = {Ness, Jose and Dominic J Cirillo and David R Weir and Nisly, Nicole L. and Robert B Wallace} } @article {6961, title = {The Economic Consequences of a Husband{\textquoteright}s Death: Evidence from the HRS and AHEAD}, journal = {Social Security Bulletin}, volume = {65}, year = {2004}, pages = {31-44}, publisher = {65}, abstract = {This article examines the economic status of older widowed women in the 1990s using the Health and Retirement Study. Widowhood remains an important risk factor for transition into poverty, although somewhat less so than 20 years ago. Despite increased labor force participation rates among women and Employee Retirement Income Security Act (ERISA) reforms, widows live with lower household earnings, pension income, and wealth than do married women. Women widowed at younger ages are at greatest risk for economic hardship after widowhood and their situation declines with the duration of widowhood. We also find that women in households that are least prepared financially for widowhood are at greatest risk of husband{\textquoteright}s death, because of the strong relationship between mortality and wealth.}, keywords = {Net Worth and Assets}, url = {https://www.ssa.gov/policy/docs/ssb/v65n3/v65n3p31.html}, author = {Purvi Sevak and David R Weir and Robert J. Willis} } @article {6921, title = {Out-of-pocket health care expenditures among older Americans with dementia.}, journal = {Alzheimer Dis Assoc Disord}, volume = {18}, year = {2004}, month = {2004 Apr-Jun}, pages = {90-8}, publisher = {18}, abstract = {

The number of older individuals with dementia will likely increase significantly in the next decades, but there is currently limited information regarding the out-of-pocket expenditures (OOPE) for medical care made by cognitively impaired individuals and their families. We used data from the 1993 and 1995 Asset and Health Dynamics Study, a nationally representative longitudinal survey of older Americans, to determine the OOPE for individuals with and without dementia. Dementia was identified in 1993 using a modified version of the Telephone Interview for Cognitive Status for self-respondents, and proxy assessment of memory and judgment for proxy respondents. In 1995, respondents reported OOPE over the prior 2 years for: 1) hospital and nursing home stays, 2) outpatient services, 3) home care, and 4) prescription medications. The adjusted mean annual OOPE was 1,350 US dollars for those without dementia, 2,150 US dollars for those with mild/moderate dementia, and 3,010 US dollars for those with severe dementia (p < 0.01). Expenditures for hospital/nursing home care (1,770 per year US dollars) and prescription medications (800 per year US dollars) were the largest OOPE components for those with severe dementia. We conclude that dementia is independently associated with significantly higher OOPE for medical care compared with those with normal cognitive function. Severe dementia is associated with a doubling of OOPE, mainly due to higher payments for long-term care. Given that the number of older Americans with dementia will likely increase significantly in the coming decades, changes in public funding aimed at reducing OOPE for both long-term care and prescription medications would have considerable impact on individuals with dementia and their families.

}, keywords = {Aged, Aged, 80 and over, Alzheimer disease, Costs and Cost Analysis, Data Interpretation, Statistical, Female, Financing, Personal, Health Care Costs, Health Expenditures, Health Surveys, Humans, Insurance Coverage, Longitudinal Studies, Male}, issn = {0893-0341}, doi = {10.1097/01.wad.0000126620.73791.3e}, author = {Kenneth M. Langa and Eric B Larson and Robert B Wallace and A. Mark Fendrick and Norman L Foster and Mohammed U Kabeto and David R Weir and Robert J. Willis and A. Regula Herzog} } @article {5496, title = {Widowhood, Divorce and Loss of Health Insurance Among Near-Elderly Women: Evidence from the Health and Retirement Study}, number = {WP2003-040}, year = {2003}, institution = {Michigan Retirement Research Center, University of Michigan}, address = {Ann Arbor, MI}, abstract = {We have found modest effects of widowhood events on loss of health insurance. There are also modest effects of widowhood on labor supply, which we have not as yet attempted to attribute to insurance demand. Even new widowhood events, however, are not random with respect to initial conditions. Both initial health insurance status and risk of future widowhood are related to basic characteristics observed when married at baseline. When these confounding variables are controlled for in models of the effect of widowhood events on uninsurance, there is no longer statistical evidence of an independent effect of husband{\textquoteright}s death on risk of losing insurance. Part of the reason why the measured independent effect of widowhood appears small is that there are events within marriage that can also affect insurance coverage, such as retirement or health events. Even though the number of uninsured women whose lack of coverage can be attributed to widowhood is therefore small, and not a distinct major policy motive for changes in age of eligibility for Medicare, uninsurance rates overall among the near elderly, and the potential public burden of cost-shifting from years just before 65 to years just after gaining Medicare coverage, suggest that Medicare eligibility policies should be a focus of continued research.}, keywords = {Adult children, Demographics, Medicare/Medicaid/Health Insurance, Net Worth and Assets, Women and Minorities}, url = {https://papers.ssrn.com/sol3/papers.cfm?abstract_id=1090894}, author = {David R Weir and Robert J. Willis} } @article {6790, title = {Informal caregiving for diabetes and diabetic complications among elderly americans.}, journal = {J Gerontol B Psychol Sci Soc Sci}, volume = {57}, year = {2002}, month = {2002 May}, pages = {S177-86}, publisher = {57B}, abstract = {

OBJECTIVES: Little is known regarding the amount of time spent by unpaid caregivers providing help to elderly individuals for disabilities associated with diabetes mellitus (DM). We sought to obtain nationally representative estimates of the time, and associated cost, of informal caregiving provided to elderly individuals with diabetes, and to determine the complications of DM that contribute most significantly to the subsequent need for informal care.

METHODS: We estimated multivariable regression models using data from the 1993 Asset and Health Dynamics Among the Oldest Old Study, a nationally representative survey of people aged 70 or older (N = 7,443), to determine the weekly hours of informal caregiving and imputed cost of caregiver time for community-dwelling elderly individuals with and without a diagnosis of DM.

RESULTS: Those without DM received an average of 6.1 hr per week of informal care, those with DM taking no medications received 10.5 hr, those with DM taking oral medications received 10.1 hr, and those with DM taking insulin received 14.4 hr of care (p <.01). Disabilities related to heart disease, stroke, and visual impairment were important predictors of diabetes-related informal care. The total cost of informal caregiving for elderly individuals with diabetes in the United States was between $3 and $6 billion per year, similar to previous estimates of the annual paid long-term care costs attributable to DM.

DISCUSSION: Diabetes imposes a substantial burden on elderly individuals, their families, and society, both through increased rates of disability and the significant time that informal caregivers must spend helping address the associated functional limitations. Future evaluations of the costs of diabetes, and the cost-effectiveness of diabetes interventions, should consider the significant informal caregiving costs associated with the disease.

}, keywords = {Aged, Aged, 80 and over, Caregivers, Cost of Illness, Costs and Cost Analysis, Diabetes Complications, Diabetes Mellitus, Disabled Persons, Female, Health Surveys, Humans, Hypoglycemic Agents, Insulin, Male, Time Factors}, issn = {1079-5014}, doi = {10.1093/geronb/57.3.s177}, author = {Kenneth M. Langa and Sandeep Vijan and Rodney A. Hayward and M.E. Chernew and Caroline S Blaum and Mohammed U Kabeto and David R Weir and Steven J. Katz and Robert J. Willis and A. Mark Fendrick} } @inbook {5128, title = {Prospects for Widow Poverty}, booktitle = {Forecasting retirement needs and retirement wealth.}, series = {Pension Research Council Publications.:}, year = {2000}, note = {ProCite field[8]: eds.}, pages = {208 -34}, publisher = {University of Pennsylvania Press}, organization = {University of Pennsylvania Press}, address = {Philadelphia}, keywords = {Consumption and Savings, Methodology, Net Worth and Assets, Retirement Planning and Satisfaction}, author = {David R Weir and Robert J. Willis}, editor = {Olivia S. Mitchell and P. Brett Hammond and Anna M. Rappaport} }