%0 Journal Article %J The International Journal of Aging and Human Development %D 2023 %T Gender and the Subjective Well-Being of Older Widows and Widowers. %A Geng, Jing %A Calasanti, Toni M %K gender repertoires %K Happiness %K inequalities %K Life Satisfaction %X

Previous research on older adults who are widowed often focuses on the immediate subjective impacts of spousal loss, and how gender might influence this. Our interest here is on the factors that influence subjective well-being after a period of at least two years' post-bereavement, and how this might differ for men and women. We draw on theoretical considerations from previous research on gender and on widowhood and use two different measures-life satisfaction and happiness-to assess possible differences in this subjective outcome. We used data from the 2014 Health and Retirement Study on 692 widowed adults aged 65 and over (578 females and 114 males) and employed regression and postestimation analyses to examine whether and how gender influences their subjective well-being. Our findings show that gender did not affect overall levels of subjective well-being, regardless of measure. However, gender did influence the predictors, such as total household income, total wealth, and social support from children and friends, for life satisfaction and happiness somewhat differently. Our study highlights the importance of examining gender differences among older widows and widowers and also underlines the importance of introducing different measures of subjective well-being that might yield different yet valuable findings.

%B The International Journal of Aging and Human Development %G eng %R 10.1177/00914150221092990 %0 Journal Article %J J Gerontol B Psychol Sci Soc Sci %D 2023 %T Gender of study partners and research participants associated with differences in study partner ratings of cognition and activity level. %A Stites, Shana D %A Gurian, Anna %A Coykendall, Cameron %A Largent, Emily A %A Harkins, Kristin %A Karlawish, Jason %A Coe, Norma B %K activity level %K Cognition %K gender %X

OBJECTIVE: Studies of Alzheimer's disease (AD) typically include "study partners" (SPs) who report on participants' cognition and function. Prior studies show SP reports differ depending on the relationship between the SP and participant, that is, spouse or adult child. Adult children SPs are typically female. Could differing reports be due to gender? Knowing this may help explain variability in measurement.

METHODS: The Aging, Demographics and Memory Study (ADAMS) enrolled a subset of participants from the Health and Retirement Study (HRS). Each participant had a SP. Bivariate and multivariable regression models compared 718 SP-participant dyads.

RESULTS: In analyses of four groups defined by SP and participant gender, dyads composed of two women were less likely to identify as White (75.8%, 95%CI 70.4 to 80.5) than dyads composed of two men (93.3%, 95%CI 81.2 to 97.8). In analyses adjusted for severity of cognitive and functional impairment, women SPs rated women participants as more active than they rated men, mean 2.15 (95%CI, 2.07 to 2.22) versus mean 2.30 (95%CI, 2.24 to 2.37), respectively, on a 4-point scale. Similarly, men SPs rated women participants as more active than they rated men, mean 2.1 (95%CI, 2.0 to 2.2) and mean 2.4 (95%CI, 2.3 to 2.5), respectively. In an analysis of cognitively unimpaired participants, women SPs rated participants' memory worse than men SPs did (p<0.05).

DISCUSSION: SP and participant gender influence SPs' reports of another person's cognition and activity level. Our findings expand what is understood about how non-disease factors influence measures of disease severity.

%B J Gerontol B Psychol Sci Soc Sci %8 2023 Feb 15 %G eng %R 10.1093/geronb/gbad026 %0 Journal Article %J Geroscience %D 2023 %T A genome-wide association study of frailty identifies significant genetic correlation with neuropsychiatric, cardiovascular, and inflammation pathways. %A Ye, Yixuan %A Noche, Rommell B %A Szejko, Natalia %A Both, Cameron P %A Acosta, Julian N %A Leasure, Audrey C %A Brown, Stacy C %A Sheth, Kevin N %A Gill, Thomas M %A Zhao, Hongyu %A Falcone, Guido J %K genome-wide. cardiovascular %K Inflammation %K neuropsychiatric %X

Frailty is an aging-related clinical phenotype defined as a state in which there is an increase in a person's vulnerability for dependency and/or mortality when exposed to a stressor. While underlying mechanisms leading to the occurrence of frailty are complex, the importance of genetic factors has not been fully investigated. We conducted a large-scale genome-wide association study (GWAS) of frailty, as defined by the five criteria (weight loss, exhaustion, physical activity, walking speed, and grip strength) captured in the Fried Frailty Score (FFS), in 386,565 European descent participants enrolled in the UK Biobank (mean age 57 [SD 8] years, 208,481 [54%] females). We identified 37 independent, novel loci associated with the FFS (p < 5 × 10), including seven loci without prior described associations with other traits. The variants associated with FFS were significantly enriched in brain tissues as well as aging-related pathways. Our post-GWAS bioinformatic analyses revealed significant genetic correlations between FFS and cardiovascular-, neurological-, and inflammation-related diseases/traits, and subsequent Mendelian Randomization analyses identified causal associations with chronic pain, obesity, diabetes, education-related traits, joint disorders, and depressive/neurological, metabolic, and respiratory diseases. The GWAS signals were replicated in the Health and Retirement Study (HRS, n = 9,720, mean age 73 [SD 7], 5,582 [57%] females), where the polygenic risk score built from UKB GWAS was significantly associated with the FFS in HRS individuals (OR per SD of the score 1.27, 95% CI 1.22-1.31, p = 1.3 × 10). These results provide new insight into the biology of frailty by comprehensively evaluating its genetic architecture.

%B Geroscience %G eng %R 10.1007/s11357-023-00771-z %0 Journal Article %J The Journals of Gerontology, Series B %D 2022 %T Gender, Age of Migration, and Cognitive Life Expectancies among Older Latinos: Evidence from the Health and Retirement Study. %A Garcia, Marc A %A Tarraf, Wassim %A Reyes, Adriana M %A Chiu, Chi-Tsun %K cognitive aging %K Migration and the Life-course %K race and ethnicity %X

OBJECTIVES: Migration and gender are important factors that differentiate the Latino immigrant experience in the United States. We investigate the association between nativity status, age of migration, and cognitive life expectancies among a nationally representative sample of Latino adults aged 50 and older to explore whether age of migration and gender influence cognitive aging across the life course.

METHODS: This study used data from the Health and Retirement Study (1998-2016) to estimate Sullivan-based life tables of cognitive life expectancies by nativity, age of migration, and gender for older Latino adults. Cognitive status was based on the Langa-Weir (LW) algorithm. We test for both within-group (i.e., nativity and age of migration) and gender differences to explore the overall burden of disease among this rapidly growing population.

RESULTS: Foreign-born Latinos, regardless of age of migration or gender, spend a greater number of years after age 50 with cognitive impairment/no dementia than U.S.-born Latinos. However, the number of years spent with dementia varied by subgroup with mid-life immigrant men and late-life immigrant men and women exhibiting a significant disadvantage relative to the U.S.-born. Furthermore, we document a gender disadvantage for all Latino women, regardless of immigrant status.

DISCUSSION: The robust relationship between nativity, age of migration, and cognitive aging suggests that older foreign-born Latinos experiencing cognitive decline may place serious burdens on families. Future research should target the needs of different subgroups of older Latinos who are entering their last decades of life to develop culturally appropriate long-term care programs.

%B The Journals of Gerontology, Series B %V 77 %P e226-e233 %G eng %N 12 %R 10.1093/geronb/gbac133 %0 Report %D 2022 %T The Gender Gap in Household Bargaining Power: A Revealed-Preference Approach %A Ran Gu %A Cameron Peng %A Weilong Zhang %K gender gap %X When members of the same household have different risk preferences, whose preference matters more for investment decisions and why? We propose an intrahousehold model that aggregates individual preferences at the household level as a result of bargaining. We structurally estimate the model, analyze the determinants of bargaining power, and find a significant gender gap. The gap is partially explained by gender differences in individual characteristics such as income and employment, but it is also driven by gender effects. These patterns hold broadly across Australia, Germany, and the US. We further link the distribution of bargaining power to perceived gender norms in the cross-section of households %C Paris, France %G eng %U https://www.weilongzhang.com/uploads/1/2/3/7/123776250/intrahh_v17.pdf %0 Journal Article %J Molecular Psychiatry %D 2022 %T Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning. %A Lahti, Jari %A Tuominen, Samuli %A Yang, Qiong %A Pergola, Giulio %A Ahmad, Shahzad %A Amin, Najaf %A Armstrong, Nicola J %A Beiser, Alexa %A Bey, Katharina %A Bis, Joshua C %A Boerwinkle, Eric %A Bressler, Jan %A Campbell, Archie %A Campbell, Harry %A Chen, Qiang %A Corley, Janie %A Cox, Simon R %A Davies, Gail %A De Jager, Philip L %A Derks, Eske M %A Jessica Faul %A Fitzpatrick, Annette L %A Fohner, Alison E %A Ford, Ian %A Fornage, Myriam %A Gerring, Zachary %A Grabe, Hans J %A Grodstein, Francine %A Gudnason, Vilmundur %A Simonsick, Eleanor %A Holliday, Elizabeth G %A Joshi, Peter K %A Kajantie, Eero %A Kaprio, Jaakko %A Karell, Pauliina %A Kleineidam, Luca %A Knol, Maria J %A Kochan, Nicole A %A Kwok, John B %A Leber, Markus %A Lam, Max %A Lee, Teresa %A Li, Shuo %A Loukola, Anu %A Luck, Tobias %A Marioni, Riccardo E %A Mather, Karen A %A Medland, Sarah %A Mirza, Saira S %A Nalls, Mike A %A Nho, Kwangsik %A O'Donnell, Adrienne %A Oldmeadow, Christopher %A Painter, Jodie %A Pattie, Alison %A Reppermund, Simone %A Risacher, Shannon L %A Rose, Richard J %A Sadashivaiah, Vijay %A Scholz, Markus %A Satizabal, Claudia L %A Schofield, Peter W %A Schraut, Katharina E %A Scott, Rodney J %A Simino, Jeannette %A Smith, Albert V %A Smith, Jennifer A %A Stott, David J %A Surakka, Ida %A Teumer, Alexander %A Thalamuthu, Anbupalam %A Trompet, Stella %A Turner, Stephen T %A van der Lee, Sven J %A Villringer, Arno %A Völker, Uwe %A Wilson, Robert S %A Wittfeld, Katharina %A Vuoksimaa, Eero %A Xia, Rui %A Yaffe, Kristine %A Yu, Lei %A Zare, Habil %A Zhao, Wei %A Ames, David %A Attia, John %A Bennett, David A %A Brodaty, Henry %A Chasman, Daniel I %A Goldman, Aaron L %A Hayward, Caroline %A Ikram, M Arfan %A Jukema, J Wouter %A Sharon L R Kardia %A Lencz, Todd %A Loeffler, Markus %A Mattay, Venkata S %A Palotie, Aarno %A Psaty, Bruce M %A Ramirez, Alfredo %A Ridker, Paul M %A Riedel-Heller, Steffi G %A Sachdev, Perminder S %A Saykin, Andrew J %A Scherer, Martin %A Schofield, Peter R %A Sidney, Stephen %A Starr, John M %A Trollor, Julian %A Ulrich, William %A Wagner, Michael %A David R Weir %A Wilson, James F %A Wright, Margaret J %A Weinberger, Daniel R %A Debette, Stéphanie %A Eriksson, Johan G %A Mosley, Thomas H %A Launer, Lenore J %A van Duijn, Cornelia M %A Deary, Ian J %A Seshadri, Sudha %A Räikkönen, Katri %K Genome %K health outcomes %K Memory %K neurocognitive outcomes %K polygenic score %K Verbal Learning %X

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.

%B Molecular Psychiatry %G eng %R 10.1038/s41380-022-01710-8 %0 Journal Article %J The Journals of Gerontology: Series B %D 2021 %T Gateway to Global Aging Data: Resources for Cross-National Comparisons of Family, Social Environment, and Healthy Aging. %A Lee, Jinkook %A Drystan F. Phillips %A Wilkens, Jenny %K Cross-Country %K Gateway to Global Aging %K social network %X

OBJECTIVES: The Gateway to Global Aging Data (Gateway; g2aging.org) is a data and information platform developed to facilitate cross-country analyses on aging, especially those using the international family of Health and Retirement studies. We provide a brief introduction to the Gateway to Global Aging Data, discussing its potential for cross-national comparisons of family, social environment, and healthy aging.

METHODS: We summarize the survey metadata, study characteristics, and harmonized data available from the Gateway, describing the population represented in each study. We portray cohort characteristics and key measures of health and social environment from 37 countries in North America, Europe, and Asia using harmonized data.

RESULTS: Significant cross-country heterogeneity was observed in many measures of family, social environment, and healthy aging indicators. For example, there was a three-fold difference in co-residence with children, ranging from 14% in Sweden to over 46% in Spain and Korea in 2014. From 2002-2014, the difference between informal care receipt in individuals of low and high wealth decreased by 6% in the US and remained unchanged in England. The percentage of individuals aged 50-59 living alone in 2012 varied fifteen-fold, from a low of 2% in China to a high of 30% in Mexico.

DISCUSSION: By partnering with nationally representative studies around the globe, the Gateway to Global Aging Data facilitates comparative research on aging through the provision of easy-to-use harmonized data files and other valuable tools.

%B The Journals of Gerontology: Series B %V 76 %P S5-S16 %G eng %N Supplement_1 %R 10.1093/geronb/gbab050 %0 Conference Proceedings %D 2021 %T The Gender Gap in Household Bargaining Power: A Portfolio-Choice Approach %A Ran Gu %A Cameron Peng %A Weilong Zhang %K gender gap %X When members of the same household have different risk preferences, whose preference matters more for investment decisions and why? We propose an intrahousehold model that aggregates individual preferences at the household level. This allows us to back out the distribution and determinants of bargaining power from household portfolio choice. We structurally estimate the model, analyze the determinants of bargaining power, and find a significant gender gap in bargaining power. While the gap is partially explained by gender differences in individual characteristics such as income and employment, it is also due to gender effects. These patterns hold broadly across Australia, Germany, and the US. We further link the distribution of bargaining power to perceived gender norms in the cross-section of households. %I SSRN %C Paris, France %G eng %R http://dx.doi.org/10.2139/ssrn.3814200 %0 Journal Article %J Mol Psychiatry %D 2021 %T Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci. %A de Las Fuentes, Lisa %A Yun Ju Sung %A Noordam, Raymond %A Thomas W Winkler %A Feitosa, Mary F %A Schwander, Karen %A Bentley, Amy R %A Brown, Michael R %A Guo, Xiuqing %A Alisa Manning %A Daniel I Chasman %A Aschard, Hugues %A Traci M Bartz %A Bielak, Lawrence F %A Campbell, Archie %A Cheng, Ching-Yu %A Dorajoo, Rajkumar %A Hartwig, Fernando P %A Horimoto, A R V R %A Li, Changwei %A Li-Gao, Ruifang %A Liu, Yongmei %A Marten, Jonathan %A Musani, Solomon K %A Ntalla, Ioanna %A Rankinen, Tuomo %A Melissa Richard %A Sim, Xueling %A Smith, Albert V %A Tajuddin, Salman M %A Bamidele O Tayo %A Vojinovic, Dina %A Warren, Helen R %A Xuan, Deng %A Alver, Maris %A Boissel, Mathilde %A Jin-Fang Chai %A Chen, Xu %A Christensen, Kaare %A Divers, Jasmin %A Evangelou, Evangelos %A Gao, Chuan %A Giorgia G Girotto %A Sarah E Harris %A He, Meian %A Hsu, Fang-Chi %A Kühnel, Brigitte %A Laguzzi, Federica %A Li, Xiaoyin %A Lyytikäinen, Leo-Pekka %A Ilja M Nolte %A Poveda, Alaitz %A Rauramaa, Rainer %A Riaz, Muhammad %A Rueedi, Rico %A Shu, Xiao-Ou %A Snieder, Harold %A Sofer, Tamar %A Takeuchi, Fumihiko %A Verweij, Niek %A Erin B Ware %A Weiss, Stefan %A Yanek, Lisa R %A Amin, Najaf %A Dan E Arking %A Donna K Arnett %A Bergmann, Sven %A Boerwinkle, Eric %A Brody, Jennifer A %A Broeckel, Ulrich %A Brumat, Marco %A Burke, Gregory %A Cabrera, Claudia P %A Canouil, Mickaël %A Chee, Miao Li %A Chen, Yii-Der Ida %A Cocca, Massimiliano %A Connell, John %A de Silva, H Janaka %A de Vries, Paul S %A Eiriksdottir, Gudny %A Jessica Faul %A Fisher, Virginia %A Forrester, Terrence %A Fox, Ervin F %A Friedlander, Yechiel %A Gao, He %A Gigante, Bruna %A Giulianini, Franco %A Gu, Chi Charles %A Gu, Dongfeng %A Tamara B Harris %A He, Jiang %A Heikkinen, Sami %A Heng, Chew-Kiat %A Hunt, Steven %A Ikram, M Arfan %A Irvin, Marguerite R %A Kähönen, Mika %A Kavousi, Maryam %A Khor, Chiea Chuen %A Kilpeläinen, Tuomas O %A Koh, Woon-Puay %A Komulainen, Pirjo %A Kraja, Aldi T %A Krieger, J E %A Langefeld, Carl D %A Li, Yize %A Liang, Jingjing %A David C Liewald %A Liu, Ching-Ti %A Liu, Jianjun %A Kurt Lohman %A Mägi, Reedik %A McKenzie, Colin A %A Meitinger, Thomas %A Andres Metspalu %A Milaneschi, Yuri %A Lili Milani %A Dennis O Mook-Kanamori %A Michael A Nalls %A Nelson, Christopher P %A Norris, Jill M %A Jeff O'Connell %A Ogunniyi, Adesola %A Padmanabhan, Sandosh %A Palmer, Nicholette D %A Nancy L Pedersen %A Thomas T Perls %A Peters, Annette %A Petersmann, Astrid %A Peyser, Patricia A %A Polasek, Ozren %A David J Porteous %A Raffel, Leslie J %A Rice, Treva K %A Rotter, Jerome I %A Rudan, Igor %A Rueda-Ochoa, Oscar-Leonel %A Sabanayagam, Charumathi %A Babatunde Salako %A Schreiner, Pamela J %A Shikany, James M %A Stephen Sidney %A Sims, Mario %A Sitlani, Colleen M %A Smith, Jennifer A %A John M Starr %A Strauch, Konstantin %A Swertz, Morris A %A Teumer, Alexander %A Tham, Yih Chung %A André G Uitterlinden %A Vaidya, Dhananjay %A van der Ende, M Yldau %A Waldenberger, Melanie %A Wang, Lihua %A Wang, Ya-Xing %A Wei, Wen-Bin %A David R Weir %A Wen, Wanqing %A Yao, Jie %A Yu, Bing %A Yu, Caizheng %A Yuan, Jian-Min %A Zhao, Wei %A Alan B Zonderman %A Becker, Diane M %A Bowden, Donald W %A Ian J Deary %A Dörr, Marcus %A Tõnu Esko %A Freedman, Barry I %A Froguel, Philippe %A Paolo P. Gasparini %A Gieger, Christian %A Jost Bruno Jonas %A Kammerer, Candace M %A Kato, Norihiro %A Lakka, Timo A %A Leander, Karin %A Lehtimäki, Terho %A Patrik K E Magnusson %A Marques-Vidal, Pedro %A Brenda W J H Penninx %A Nilesh J Samani %A van der Harst, Pim %A Wagenknecht, Lynne E %A Wu, Tangchun %A Zheng, Wei %A Zhu, Xiaofeng %A Bouchard, Claude %A Cooper, Richard S %A Correa, Adolfo %A Michele K Evans %A Gudnason, Vilmundur %A Caroline Hayward %A Horta, Bernardo L %A Tanika N Kelly %A Stephen B Kritchevsky %A Levy, Daniel %A Walter R Palmas %A Pereira, A C %A Province, Michael M %A Psaty, Bruce M %A Ridker, Paul M %A Charles N Rotimi %A Tai, E Shyong %A van Dam, Rob M %A Cornelia M van Duijn %A Wong, Tien Yin %A Kenneth Rice %A Gauderman, W James %A Alanna C Morrison %A Kari E North %A Sharon L R Kardia %A Caulfield, Mark J %A Elliott, Paul %A Munroe, Patricia B %A Franks, Paul W %A Rao, Dabeeru C %A Myriam Fornage %K Blood pressure %K Epistasis, Genetic %K Genetic Loci %K Genome-Wide Association Study %K Humans %K Hypertension %K Polymorphism, Single Nucleotide %X

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 × 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.

%B Mol Psychiatry %V 26 %P 2111-2125 %G eng %N 6 %R 10.1038/s41380-020-0719-3 %0 Journal Article %J Journal of the American Geriatrics Society %D 2021 %T Geriatric Syndromes and Atrial Fibrillation: Prevalence and Association with Anticoagulant Use in a National Cohort of Older Americans. %A Sachin J Shah %A Margaret C Fang %A Sun Y Jeon %A Gregorich, Steven E %A Kenneth E Covinsky %K anticoagulants %K Atrial Fibrillation %K Epidemiology %K geriatric syndromes %X

BACKGROUND: Although guidelines recommend focusing primarily on stroke risk to recommend anticoagulants in atrial fibrillation (AF), physicians report that geriatric syndromes (e.g., falls and disability) are important when considering anticoagulants. Little is known about the prevalence of geriatric syndromes in older adults with AF or the association with anticoagulant use.

METHODS: We performed a cross-sectional analysis of the 2014 Health and Retirement Study, a nationally representative study of older Americans. Participants were asked questions to assess domains of aging, including function, cognition, and medical conditions. We included participants 65 years and older with 2 years of continuous Medicare enrollment who met AF diagnosis criteria by claims codes. We examined five geriatric syndromes: one or more falls within the last 2 years, receiving help with activities of daily living (ADLs) or instrumental ADLs (IADL), experienced incontinence, and cognitive impairment. We determined the prevalence of geriatric syndromes and their association with anticoagulant use, adjusting for ischemic stroke risk (i.e., CHA DS -VASc score [congestive heart failure, hypertension, age, diabetes mellitus, stroke, vascular disease, and sex]).

RESULTS: In this study of 779 participants with AF (median age = 80 years; median CHA DS -VASc score = 4), 82% had one or more geriatric syndromes. Geriatric syndromes were common: 49% reported falls, 38% had ADL impairments, 42% had IADL impairments, 37% had cognitive impairments, and 43% reported incontinence. Overall, 65% reported anticoagulant use; guidelines recommend anticoagulant use for 97% of participants. Anticoagulant use rate decreased for each additional geriatric syndrome (average marginal effect = -3.7%; 95% confidence interval = -1.4% to -5.9%). Lower rates of anticoagulant use were reported in participants with ADL dependency, IADL dependency, and dementia.

CONCLUSION: Most older adults with AF had at least one geriatric syndrome, and geriatric syndromes were associated with reduced anticoagulant use. The high prevalence of geriatric syndromes may explain the lower than expected anticoagulant use in older adults.

%B Journal of the American Geriatrics Society %V 69 %P 349-356 %G eng %N 2 %R 10.1111/jgs.16822 %0 Journal Article %J Translational Psychiatry %D 2020 %T Genome-wide association study of cognitive function in diverse Hispanics/Latinos: results from the Hispanic Community Health Study/Study of Latinos. %A Jian, Xueqiu %A Sofer, Tamar %A Wassim Tarraf %A Bressler, Jan %A Jessica Faul %A Zhao, Wei %A Scott M Ratliff %A Lamar, Melissa %A Lenore J Launer %A Laurie, Cathy C %A Schneiderman, Neil %A David R Weir %A Wright, Clinton B %A Kristine Yaffe %A Zeng, Donglin %A DeCarli, Charles %A Thomas H Mosley %A Smith, Jennifer A %A Hector M González %A Myriam Fornage %K Aged %K Cognition %K Genome-Wide Association Study %K Hispanic or Latino %K Humans %K Middle Aged %K Neuropsychological tests %K Public Health %K Ubiquitin-Conjugating Enzymes %X

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.

%B Translational Psychiatry %V 10 %P 245 %G eng %N 1 %R 10.1038/s41398-020-00930-2 %0 Journal Article %J Research in Human Development %D 2020 %T Glycosylated Hemoglobin Level, Race/Ethnicity, and Cognition in Midlife and Early Old Age %A Ortiz, Kasim %A Marc Garcia %A Emily Briceño %A Diminich, Erica D. %A Arévalo, Sandra P. %A Vega, Irving E. %A Wassim Tarraf %K biomarker data %K cognitive function %K Racial/ethnic differences %X Empirical evidence linking racial/ethnic differences in glycosylated hemoglobin levels (HbA1c) to cognitive function in midlife and early old age is limited. We use biomarker data from the Health and Retirement Study (HRS, 2006?2014), on adults 50?64 years at baseline (57?73 years by 2014), and fit multinomial logistic regression models to assess the association between baseline HbA1c, cognitive function (using Langa?Weir classifications) and mortality across 8 years. Additionally, we test for modification effects by race/ethnicity. In age- and sex-adjusted models high HbA1c level was associated with lower baseline cognition and higher relative risk ratios (RRR; vs. normal cognition) for cognitive impairment no dementia (CIND; RRR = 2.3; 95%CI = [1.38;3.84]; p < .01), and dementia (RRR = 4.00; 95%CI = [1.76;9.10]; p < .01). Adjusting for sociodemographic, behavioral risk factors, and other health conditions explained the higher RRR for CIND and attenuated the RRR for dementia by approximately 30%. HbA1c levels were not linked to the slope of cognitive decline, and we found no evidence of modification effects for HbA1c by race/ethnicity. Targeting interventions for glycemic control in the critical midlife period can protect baseline cognition and buffer against downstream development of cognitive impairment. This can yield important public health benefits and reductions in burdens associated with cognitive impairment, particularly among race/ethnic minorities who are at higher risk for metabolic diseases. %B Research in Human Development %V 17 %P 20 - 40 %@ 1542-7609 %G eng %N 1 %R 10.1080/15427609.2020.1743810 %0 Journal Article %J Journal of Clinical Endocrinology and Metabolism %D 2019 %T Glycated hemoglobin and all-cause and cause-specific mortality among adults with and without diabetes. %A Li, Fu-Rong %A Zhang, Xi-Ru %A Zhong, Wen-Fang %A Li, Zhi-Hao %A Gao, Xiang %A Virginia Byers Kraus %A Lv, Yue-Bin %A Zou, Meng-Chen %A Chen, Guo-Chong %A Chen, Pei-Liang %A Zhang, Min-Yi %A Kur, Akech Kuol Akech %A Shi, Xiao-Ming %A Wu, Xian-Bo %A Mao, Chen %K Biomarkers %K Diabetes %K Mortality %X

CONTEXT: The patterns of associations between glycated hemoglobin (HbA1c) and mortality are still unclear.

OBJECTIVE: To explore the extent to which ranges of HbA1c levels are associated with the risk of mortality among participants with and without diabetes.

DESIGN: Setting and patients: This was a nationwide, community-based prospective cohort study. Included were 15,869 participants (median age 64 years) of the Health and Retirement Study, with available HbA1c data and without a history of cancer. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidential intervals (95% CIs) for mortality.

RESULTS: A total of 2,133 participants died during a median follow-up of 5.8 years. In participants with diabetes, those with an HbA1c level of 6.5% were at the lowest risk of all-cause mortality. When HbA1c level was lower than 5.6% or higher than 7.4%, the increased all-cause mortality risk became statistically significant as compared with an HbA1c level of 6.5%. As for participants without diabetes, those with an HbA1c level of 5.4% were at the lowest risk of all-cause mortality. When HbA1c level was lower than 5.0%, the increased all-cause mortality risk became statistically significant as compared with an HbA1c level of 5.4%. However, we did not observe a statistically significant elevated risk of all-cause mortality above an HbA1c level of 5.4%.

CONCLUSIONS: A U-shaped and a reverse J-shaped association for all-cause mortality were found among participants with and without diabetes. The corresponding Optimal ranges for overall survival are predicted to be 5.6-7.4% and 5.0-6.5%, respectively.

%B Journal of Clinical Endocrinology and Metabolism %G eng %1 http://www.ncbi.nlm.nih.gov/pubmed/30896760?dopt=Abstract %R 10.1210/jc.2018-02536 %0 Journal Article %J Social Science Research %D 2019 %T The growing American health penalty: International trends in the employment of older workers with poor health %A Ben Baumberg Geiger %A René Böheim %A Thomas Leoni %K Disability %K Employment %K health %K Panel data %K Social Security %K Welfare %X Many countries have reduced the generosity of sickness and disability programs while making them more activating – yet few studies have examined how employment rates have subsequently changed. We present estimates of how employment rates of older workers with poor health in 13 high-income countries changed 2004–7 to 2012–15 using HRS/SHARE/ELSA data. We find that those in poor health in the USA have experienced a unique deterioration: they have not only seen a widening gap to the employment rates of those with good health, but their employment rates fell per se. We find only for Sweden (and possibly England) signs that the health employment gap shrank, with rising employment but stable gaps elsewhere. We then examine possible explanations for the development in the USA: we find no evidence it links to labor market trends, but possible links to the USA's lack of disability benefit reform and wider economic trends. %B Social Science Research %V 82 %P 18 - 32 %G eng %U http://www.sciencedirect.com/science/article/pii/S0049089X1830560X %R https://doi.org/10.1016/j.ssresearch.2019.03.008 %0 Journal Article %J Journal of Marriage and Family %D 2018 %T Gender, Spousal Caregiving, and Depression: Does Paid Work Matter? %A Glauber, Rebecca %A Day, Melissa D. %K Caregiving %K Depressive symptoms %K Gender Differences %K Purpose in life %K Social Support %X Studies have shown that spousal caregiving leads to psychological distress, but few have analyzed the moderating effect of paid work. Using the 2000 to 2012 Health and Retirement Study and two-stage least squares regression models, this study found that caregiving increased women's and men's depressive symptoms. Ordinary least squares models showed that caregiving had more adverse effects on women's mental health than on men's, but these differences were eliminated in two-stage least squares models that accounted for the bidirectional effects of depression and caregiving. The current study also found that for women, part-time work attenuated the depressive effect of spousal caregiving, whereas for men, part-time work exacerbated it. These gender differences persisted even for intensive spousal caregivers. The authors suggest that caregiving women who work part-time may benefit from work-related resources. Caregiving men who work part-time, however, may feel distressed, as their work-family experiences conflict with traditional gender norms. %B Journal of Marriage and Family %V 80 %P 537-554 %G eng %N 2 %! Fam Relat %R 10.1111/jomf.2018.80.issue-210.1111/jomf.12446 %0 Journal Article %J Nature Genetics %D 2018 %T Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence %A Savage, Jeanne E. %A Philip R Jansen %A Stringer, Sven %A Watanabe, Kyoko %A Bryois, Julien %A Christiaan de Leeuw %A Nagel, Mats %A Awasthi, Swapnil %A Barr, Peter B. %A Coleman, Jonathan R. I. %A Grasby, Katrina L. %A Anke R Hammerschlag %A Kaminski, Jakob A. %A Karlsson, Robert %A Krapohl, Eva %A Lam, Max %A Nygaard, Marianne %A Chandra A Reynolds %A Joey W Trampush %A Young, Hannah %A Zabaneh, Delilah %A Hägg, Sara %A Narelle K Hansell %A Ida Karlsson %A Linnarsson, Sten %A Grant W Montgomery %A Muñoz-Manchado, Ana B. %A Quinlan, Erin B. %A Schumann, Gunter %A Skene, Nathan G. %A Webb, Bradley T. %A White, Tonya %A Dan E Arking %A Avramopoulos, Dimitrios %A Robert M Bilder %A Bitsios, Panos %A Katherine E Burdick %A Tyrone D. Cannon %A Chiba-Falek, Ornit %A Christoforou, Andrea %A Elizabeth T. Cirulli %A Congdon, Eliza %A Corvin, Aiden %A Gail Davies %A Ian J Deary %A DeRosse, Pamela %A Dickinson, Dwight %A Djurovic, Srdjan %A Donohoe, Gary %A Conley, Emily Drabant %A Johan G Eriksson %A Espeseth, Thomas %A Nelson A. Freimer %A Giakoumaki, Stella %A Giegling, Ina %A Gill, Michael %A David C. Glahn %A Ahmad R Hariri %A Hatzimanolis, Alex %A Matthew C Keller %A Knowles, Emma %A Koltai, Deborah %A Konte, Bettina %A Lahti, Jari %A Stephanie Le Hellard %A Lencz, Todd %A David C Liewald %A London, Edythe %A Astri J Lundervold %A Anil K. Malhotra %A Melle, Ingrid %A Morris, Derek %A Anna C Need %A William E R Ollier %A Aarno Palotie %A Payton, Antony %A Pendleton, Neil %A Russell A Poldrack %A Katri Räikkönen %A Reinvang, Ivar %A Roussos, Panos %A Rujescu, Dan %A Fred W Sabb %A Matthew A Scult %A Smeland, Olav B. %A Smyrnis, Nikolaos %A John M Starr %A Vidar M Steen %A Nikos C Stefanis %A Richard E Straub %A Sundet, Kjetil %A Henning Tiemeier %A Aristotle N Voineskos %A Daniel R Weinberger %A Elisabeth Widen %A Yu, Jin %A Gonçalo R Abecasis %A Andreassen, Ole A. %A Breen, Gerome %A Christiansen, Lene %A Debrabant, Birgit %A Danielle M. Dick %A Heinz, Andreas %A Hjerling-Leffler, Jens %A Mohammed Arfan Ikram %A Kendler, Kenneth S. %A Nicholas G Martin %A Sarah E Medland %A Nancy L Pedersen %A Plomin, Robert %A Tinca J Polderman %A Ripke, Stephan %A van der Sluis, Sophie %A Patrick F. Sullivan %A Scott Vrieze %A Margaret J Wright %A Posthuma, Danielle %K Genome-Wide Association Study %K Intelligence %K Meta-analyses %X Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders. %B Nature Genetics %V 50 %P 912 - 919 %8 Jan-07-2018 %G eng %U http://www.nature.com/articles/s41588-018-0152-6http://www.nature.com/articles/s41588-018-0152-6.pdfhttp://www.nature.com/articles/s41588-018-0152-6http://www.nature.com/articles/s41588-018-0152-6.pdf %N 7 %! Nat Genet %R 10.1038/s41588-018-0152-6 %0 Journal Article %J Molecular Psychiatry %D 2018 %T A genome-wide association study for extremely high intelligence %A Zabaneh, D %A Krapohl, E %A Gaspar, H A %A Curtis, C %A Lee, S H %A Patel, H %A Newhouse, S %A Wu, H M %A Simpson, M A %A Putallaz, M %A Lubinski, D %A Plomin, R %A Breen, G %K Cognitive Ability %K Education %K Genome %K Hereditary %K Humans %X We used a case-control genome-wide association (GWA) design with cases consisting of 1238 individuals from the top 0.0003 (~170 mean IQ) of the population distribution of intelligence and 8172 unselected population-based controls. The single-nucleotide polymorphism heritability for the extreme IQ trait was 0.33 (0.02), which is the highest so far for a cognitive phenotype, and significant genome-wide genetic correlations of 0.78 were observed with educational attainment and 0.86 with population IQ. Three variants in locus ADAM12 achieved genome-wide significance, although they did not replicate with published GWA analyses of normal-range IQ or educational attainment. A genome-wide polygenic score constructed from the GWA results accounted for 1.6% of the variance of intelligence in the normal range in an unselected sample of 3414 individuals, which is comparable to the variance explained by GWA studies of intelligence with substantially larger sample sizes. The gene family plexins, members of which are mutated in several monogenic neurodevelopmental disorders, was significantly enriched for associations with high IQ. This study shows the utility of extreme trait selection for genetic study of intelligence and suggests that extremely high intelligence is continuous genetically with normal-range intelligence in the population. %B Molecular Psychiatry %V 23 %P 1226 - 1232 %8 Apr-05-2018 %G eng %U http://www.nature.com/doifinder/10.1038/mp.2017.121http://www.nature.com/doifinder/10.1038/mp.2017.121 %N 5 %! Mol Psychiatry %R 10.1038/mp.2017.121 %0 Journal Article %J Res Aging %D 2017 %T Gender Differences in Spousal Care Across the Later Life Course. %A Glauber, Rebecca %K Activities of Daily Living %K Aged %K Caregivers %K Cross-Sectional Studies %K Employment %K Female %K Home Care Services %K Humans %K Male %K Marriage %K Middle Aged %K Sex Factors %K Spouses %X

Spouses often serve as the primary caregivers to their ill or disabled partners. Studies have shown that men receive more care from their wives than vice versa, but few studies have focused on how the gender gap in care varies across the later life course. Drawing on data from the Health and Retirement Study, this study examined the moderating effects of age, gender, and full-time employment on married women's and men's receipt of spousal care. This study found that among community-dwelling married adults, the gender gap in care was larger among those in middle age (50-65) than it was among those in older age. As women and men aged, the gender gap decreased primarily because men left full-time work and increased the amount of time that they spent caring for their wives. As gender differences in full-time employment narrowed, the gender gap in spousal care narrowed.

%B Res Aging %V 39 %P 934-959 %8 2017 09 %G eng %U http://www.ncbi.nlm.nih.gov/pubmed/27193046 %N 8 %1 http://www.ncbi.nlm.nih.gov/pubmed/27193046?dopt=Abstract %R 10.1177/0164027516644503 %0 Journal Article %J Int J Environ Res Public Health %D 2017 %T Gene-by-Psychosocial Factor Interactions Influence Diastolic Blood Pressure in European and African Ancestry Populations: Meta-Analysis of Four Cohort Studies. %A Wei Zhao %A Yasutake, Kalyn %A August, Carmella %A Scott M Ratliff %A Jessica Faul %A Boerwinkle, Eric %A Chakravarti, Aravinda %A Ana V. Diez-Roux %A Gao, Yan %A Michael E Griswold %A Gerardo Heiss %A Sharon L R Kardia %A Alanna C Morrison %A Musani, Solomon K %A Mwasongwe, Stanford %A Kari E North %A Rose, Kathryn M %A Sims, Mario %A Yan V Sun %A David R Weir %A Belinda L Needham %K Blood pressure %K Genetics %K GWAS %K Meta-analyses %K Psychosocial %K Socioeconomic factors %X 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. %B Int J Environ Res Public Health %V 14 %G eng %N 12 %1 http://www.ncbi.nlm.nih.gov/pubmed/29258278?dopt=Abstract %R 10.3390/ijerph14121596 %0 Journal Article %J Nature Communications %D 2017 %T Genetic architecture of epigenetic and neuronal ageing rates in human brain regions %A Lu, Ake T %A Hannon, Eilis %A Morgan E. Levine %A Eileen M. Crimmins %A Lunnon, Katie %A Mill, Jonathan %A Daniel H. Geschwind %A Horvath, Steve %K Genetics %X Identifying genes regulating the pace of epigenetic ageing represents a new frontier in genome-wide association studies (GWASs). Here using 1,796 brain samples from 1,163 individuals, we carry out a GWAS of two DNA methylation-based biomarkers of brain age: the epigenetic ageing rate and estimated proportion of neurons. Locus 17q11.2 is significantly associated (P=4.5 × 10 -9 ) with the ageing rate across five brain regions and harbours a cis-expression quantitative trait locus for EFCAB5 (P=3.4 × 10-20 ). Locus 1p36.12 is significantly associated (P=2.2 × 10-8 ) with epigenetic ageing of the prefrontal cortex, independent of the proportion of neurons. Our GWAS of the proportion of neurons identified two genome-wide significant loci (10q26 and 12p13.31) and resulted in a gene set that overlaps significantly with sets found by GWAS of age-related macular degeneration (P=1.4 × 10 -12 ), ulcerative colitis (P<1.0 × 10-20 ), type 2 diabetes (P=2.8 × 10-13 ), hip/waist circumference in men (P=1.1 × 10-9 ), schizophrenia (P=1.6 × 10-9 ), cognitive decline (P=5.3 × 10-4 ) and Parkinson's disease (P=8.6 × 10-3 ). %B Nature Communications %V 8 %8 Jun-05-2018 %G eng %U http://www.nature.com/doifinder/10.1038/ncomms15353http://www.nature.com/doifinder/10.1038/ncomms15353 %! Nat Comms %R 10.1038/ncomms15353 %0 Journal Article %J PLoS One %D 2017 %T Genetic variants specific to aging-related verbal memory: Insights from GWASs in a population-based cohort. %A Thalida E. Arpawong %A Pendleton, Neil %A Mekli, Krisztina %A John J McArdle %A Margaret Gatz %A Armoskus, Chris %A James A Knowles %A Carol A Prescott %K Cognitive Ability %K Genetics %K GWAS %K Memory %X Verbal memory is typically studied using immediate recall (IR) and delayed recall (DR) scores, although DR is dependent on IR capability. Separating these components may be useful for deciphering the genetic variation in age-related memory abilities. This study was conducted to (a) construct individual trajectories in IR and independent aspects of delayed recall, or residualized-DR (rDR), across older adulthood; and (b) identify genetic markers that contribute to four estimated phenotypes: IR and rDR levels and changes after age 60. A cognitively intact sample (N = 20,650 with 125,164 observations) was drawn from the U.S. Health and Retirement Study, a nationally representative study of adults aged 50 and older. Mixed effects regression models were constructed using repeated measures from data collected every two years (1996-2012) to estimate level at age 60 and change in memory post-60 in IR and rDR. Genome-wide association scans (GWAS) were conducted in the genotypic subsample (N = 7,486) using ~1.2 million single nucleotide polymorphisms (SNPs). One SNP (rs2075650) in TOMM40 associated with rDR level at the genome-wide level (p = 5.0x10-08), an effect that replicated in an independent sample from the English Longitudinal Study on Ageing (N = 6,898 with 41,328 observations). Meta-analysis of rDR level confirmed the association (p = 5.0x10-11) and identified two others in TOMM40 (rs71352238 p = 1.0x10-10; rs157582 p = 7.0x10-09), and one in APOE (rs769449 p = 3.1 x10-12). Meta-analysis of IR change identified associations with three of the same SNPs in TOMM40 (rs157582 p = 8.3x10-10; rs71352238 p = 1.9x10-09) and APOE (rs769449 p = 2.2x10-08). Conditional analyses indicate GWAS signals on rDR level were driven by APOE, whereas signals on IR change were driven by TOMM40. Additionally, we found that TOMM40 had effects independent of APOE e4 on both phenotypes. Findings from this first U.S. population-based GWAS study conducted on both age-related immediate and delayed verbal memory merit continued examination in other samples and additional measures of verbal memory. %B PLoS One %V 12 %P e0182448 %8 2017 %G eng %N 8 %1 http://www.ncbi.nlm.nih.gov/pubmed/28800603?dopt=Abstract %R 10.1371/journal.pone.0182448 %0 Journal Article %J Neuropsychopharmacology %D 2017 %T Genome-Wide Association Study of Loneliness Demonstrates a Role for Common Variation. %A Gao, Jianjun %A Lea K. Davis %A Amy B. Hart %A Sanchez-Roige, Sandra %A Han, Lide %A John T. Cacioppo %A Abraham A Palmer %K Aged %K depression %K Extraversion, Psychological %K Female %K Genome-Wide Association Study %K Humans %K Loneliness %K Male %K Mental Disorders %K Middle Aged %K Neuroticism %K Phenotype %X

Loneliness is a complex biological trait that has been associated with numerous negative health outcomes. The measurement and environmental determinants of loneliness are well understood, but its genetic basis is not. Previous studies have estimated the heritability of loneliness between 37 and 55% using twins and family-based approaches, and have explored the role of specific candidate genes. We used genotypic and phenotypic data from 10 760 individuals aged ⩾50 years that were collected by the Health and Retirement Study (HRS) to perform the first genome-wide association study of loneliness. No associations reached genome-wide significance (p>5 × 10). Furthermore, none of the previously published associations between variants within candidate genes (BDNF, OXTR, RORA, GRM8, CHRNA4, IL-1A, CRHR1, MTHFR, DRD2, APOE) and loneliness were replicated (p>0.05), despite our much larger sample size. We estimated the chip heritability of loneliness and examined coheritability between loneliness and several personality and psychiatric traits. Our estimates of chip heritability (14-27%) support a role for common genetic variation. We identified strong genetic correlations between loneliness, neuroticism, and a scale of 'depressive symptoms.' We also identified weaker evidence for coheritability with extraversion, schizophrenia, bipolar disorder, and major depressive disorder. We conclude that loneliness, as defined in this study, is a modestly heritable trait that has a highly polygenic genetic architecture. The coheritability between loneliness and neuroticism may reflect the role of negative affectivity that is common to both traits. Our results also reflect the value of studies that probe the common genetic basis of salutary social bonds and clinically defined psychiatric disorders.

%B Neuropsychopharmacology %V 42 %P 811-821 %8 2017 Mar %G eng %U http://www.nature.com/doifinder/10.1038/npp.2016.197 %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/27629369?dopt=Abstract %! Neuropsychopharmacology %R 10.1038/npp.2016.197 %0 Journal Article %J Nature Communications %D 2017 %T Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity. %A Joshi, Peter K %A Nicola Pirastu %A Kentistou, Katherine A %A Fischer, Krista %A Edith Hofer %A Schraut, Katharina E %A Clark, David W %A Nutile, Teresa %A Barnes, Catriona L K %A Paul Rhj Timmers %A Shen, Xia %A Gandin, Ilaria %A McDaid, Aaron F %A Hansen, Thomas Folkmann %A Gordon, Scott D %A Giulianini, Franco %A Boutin, Thibaud S %A Abdellaoui, Abdel %A Zhao, Wei %A Medina-Gomez, Carolina %A Traci M Bartz %A Trompet, Stella %A Leslie A Lange %A Raffield, Laura %A van der Spek, Ashley %A Galesloot, Tessel E %A Proitsi, Petroula %A Yanek, Lisa R %A Bielak, Lawrence F %A Payton, Antony %A Murgia, Federico %A Concas, Maria Pina %A Biino, Ginevra %A Tajuddin, Salman M %A Seppälä, Ilkka %A Amin, Najaf %A Boerwinkle, Eric %A Børglum, Anders D %A Campbell, Archie %A Ellen W Demerath %A Demuth, Ilja %A Jessica Faul %A Ford, Ian %A Gialluisi, Alessandro %A Gögele, Martin %A Graff, Mariaelisa %A Aroon Hingorani %A Jouke-Jan Hottenga %A Hougaard, David M %A Hurme, Mikko A %A Ikram, M Arfan %A Jylhä, Marja %A Kuh, Diana %A Ligthart, Lannie %A Lill, Christina M %A Lindenberger, Ulman %A Lumley, Thomas %A Mägi, Reedik %A Marques-Vidal, Pedro %A Sarah E Medland %A Lili Milani %A Nagy, Reka %A William E R Ollier %A Peyser, Patricia A %A Pramstaller, Peter P %A Ridker, Paul M %A Fernando Rivadeneira %A Ruggiero, Daniela %A Saba, Yasaman %A Schmidt, Reinhold %A Schmidt, Helena %A Slagboom, P Eline %A Smith, Blair H %A Smith, Jennifer A %A Sotoodehnia, Nona %A Steinhagen-Thiessen, Elisabeth %A van Rooij, Frank J A %A Verbeek, André L %A Vermeulen, Sita H %A Vollenweider, Peter %A Wang, Yunpeng %A Werge, Thomas %A Whitfield, John B %A Alan B Zonderman %A Lehtimäki, Terho %A Michele K Evans %A Pirastu, Mario %A Fuchsberger, Christian %A Bertram, Lars %A Pendleton, Neil %A Sharon L R Kardia %A Ciullo, Marina %A Becker, Diane M %A Wong, Andrew %A Psaty, Bruce M %A Cornelia M van Duijn %A Wilson, James G %A Jukema, J Wouter %A Lambertus A Kiemeney %A André G Uitterlinden %A Franceschini, Nora %A Kari E North %A David R Weir %A Andres Metspalu %A Dorret I Boomsma %A Caroline Hayward %A Daniel I Chasman %A Nicholas G Martin %A Sattar, Naveed %A Campbell, Harry %A Tõnu Esko %A Kutalik, Zoltán %A James F Wilson %K Alleles %K Body Mass Index %K Coronary Disease %K Education %K Genetic Predisposition to Disease %K Genome-Wide Association Study %K HLA-DQ alpha-Chains %K HLA-DRB1 Chains %K Humans %K Insulin Resistance %K Life Style %K Lipoprotein(a) %K Lipoproteins, HDL %K Longevity %K Lung Neoplasms %K Obesity %K Polymorphism, Single Nucleotide %K Smoking %K Socioeconomic factors %X

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' 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.

%B Nature Communications %V 8 %P 910 %G eng %N 1 %R 10.1038/s41467-017-00934-5 %0 Journal Article %J Nat Commun %D 2016 %T Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function. %A Pattaro, Cristian %A Teumer, Alexander %A Gorski, Mathias %A Chu, Audrey Y %A Li, Man %A Mijatovic, Vladan %A Garnaas, Maija %A Tin, Adrienne %A Sorice, Rossella %A Yong Li %A Taliun, Daniel %A Olden, Matthias %A Foster, Meredith %A Qiong Yang %A Chen, Ming-Huei %A Pers, Tune H %A Andrew D Johnson %A Ko, Yi-An %A Fuchsberger, Christian %A Bamidele O Tayo %A Michael A Nalls %A Feitosa, Mary F %A Isaacs, Aaron %A Dehghan, Abbas %A d'Adamo, Pio %A Adebawole Adeyemo %A Dieffenbach, Aida Karina %A Alan B Zonderman %A Ilja M Nolte %A van der Most, Peter J %A Alan F Wright %A Alan R Shuldiner %A Alanna C Morrison %A Hofman, Albert %A Albert Vernon Smith %A Dreisbach, Albert W %A Franke, Andre %A André G Uitterlinden %A Andres Metspalu %A Tönjes, Anke %A Lupo, Antonio %A Robino, Antonietta %A Johansson, Åsa %A Demirkan, Ayse %A Kollerits, Barbara %A Freedman, Barry I %A Ponte, Belen %A Ben A Oostra %A Paulweber, Bernhard %A Krämer, Bernhard K %A Mitchell, Braxton D %A Buckley, Brendan M %A Peralta, Carmen A %A Caroline Hayward %A Helmer, Catherine %A Charles N Rotimi %A Shaffer, Christian M %A Müller, Christian %A Cinzia Felicita Sala %A Cornelia M van Duijn %A Saint-Pierre, Aude %A Daniel Ackermann %A Daniel Shriner %A Ruggiero, Daniela %A Toniolo, Daniela %A Lu, Yingchang %A Cusi, Daniele %A Czamara, Darina %A Ellinghaus, David %A David S Siscovick %A Ruderfer, Douglas %A Gieger, Christian %A Grallert, Harald %A Rochtchina, Elena %A Atkinson, Elizabeth J %A Holliday, Elizabeth G %A Boerwinkle, Eric %A Salvi, Erika %A Erwin P Bottinger %A Murgia, Federico %A Fernando Rivadeneira %A Ernst, Florian %A Kronenberg, Florian %A Hu, Frank B %A Navis, Gerjan J %A Curhan, Gary C %A Georg B Ehret %A Homuth, Georg %A Coassin, Stefan %A Thun, Gian-Andri %A Pistis, Giorgio %A Gambaro, Giovanni %A Malerba, Giovanni %A Grant W Montgomery %A Guðny Eiríksdóttir %A Jacobs, Gunnar %A Guo Li %A Wichmann, H-Erich %A Campbell, Harry %A Schmidt, Helena %A Wallaschofski, Henri %A Völzke, Henry %A Brenner, Hermann %A Kroemer, Heyo K %A Kramer, Holly %A Lin, Honghuang %A Irene Mateo Leach %A Ford, Ian %A Guessous, Idris %A Rudan, Igor %A Prokopenko, Inga %A Ingrid B Borecki %A Iris M Heid %A Kolcic, Ivana %A Persico, Ivana %A Jukema, J Wouter %A James F Wilson %A Felix, Janine F %A Divers, Jasmin %A Lambert, Jean-Charles %A Stafford, Jeanette M %A Gaspoz, Jean-Michel %A Jennifer A Smith %A Jessica Faul %A Wang, Jie Jin %A Ding, Jingzhong %A Joel N Hirschhron %A John R. Attia %A Whitfield, John B %A Chalmers, John %A Viikari, Jorma %A Coresh, Josef %A Denny, Joshua C %A Karjalainen, Juha %A Fernandes, Jyotika K %A Endlich, Karlhans %A Butterbach, Katja %A Keene, Keith L %A Kurt Lohman %A Portas, Laura %A Lenore J Launer %A Lyytikäinen, Leo-Pekka %A Yengo, Loic %A Lude L Franke %A Luigi Ferrucci %A Rose, Lynda M %A Kedenko, Lyudmyla %A Rao, Madhumathi %A Struchalin, Maksim %A Kleber, Marcus E %A Cavalieri, Margherita %A Haun, Margot %A Marilyn C Cornelis %A Ciullo, Marina %A Pirastu, Mario %A de Andrade, Mariza %A McEvoy, Mark A %A Woodward, Mark %A Adam, Martin %A Cocca, Massimiliano %A Nauck, Matthias %A Imboden, Medea %A Waldenberger, Melanie %A Pruijm, Menno %A Metzger, Marie %A Stumvoll, Michael %A Michele K Evans %A Sale, Michele M %A Kähönen, Mika %A Boban, Mladen %A Bochud, Murielle %A Rheinberger, Myriam %A Verweij, Niek %A Bouatia-Naji, Nabila %A Nicholas G Martin %A Nicholas D Hastie %A Nicole M Probst-Hensch %A Soranzo, Nicole %A Devuyst, Olivier %A Olli T Raitakari %A Gottesman, Omri %A Franco, Oscar H %A Polasek, Ozren %A Paolo P. Gasparini %A Munroe, Patricia B %A Ridker, Paul M %A Mitchell, Paul %A Muntner, Paul %A Meisinger, Christa %A Johannes H Smit %A Kovacs, Peter %A Wild, Philipp S %A Froguel, Philippe %A Rettig, Rainer %A Mägi, Reedik %A Biffar, Reiner %A Schmidt, Reinhold %A Middelberg, Rita P S %A Carroll, Robert J %A Brenda W J H Penninx %A Rodney J Scott %A Katz, Ronit %A Sedaghat, Sanaz %A Sarah Wild %A Sharon L R Kardia %A Ulivi, Sheila %A Hwang, Shih-Jen %A Enroth, Stefan %A Kloiber, Stefan %A Trompet, Stella %A Stengel, Benedicte %A Hancock, Stephen J %A Stephen T Turner %A Rosas, Sylvia E %A Stracke, Sylvia %A Tamara B Harris %A Zeller, Tanja %A Zemunik, Tatijana %A Lehtimäki, Terho %A Illig, Thomas %A Aspelund, Thor %A Nikopensius, Tiit %A Tõnu Esko %A Toshiko Tanaka %A Gyllensten, Ulf %A Völker, Uwe %A Emilsson, Valur %A Vitart, Veronique %A Aalto, Ville %A Gudnason, Vilmundur %A Chouraki, Vincent %A Chen, Wei-Min %A Igl, Wilmar %A März, Winfried %A Koenig, Wolfgang %A Lieb, Wolfgang %A Ruth J F Loos %A Yongmei Liu %A Snieder, Harold %A Pramstaller, Peter P %A Parsa, Afshin %A Jeff O'Connell %A Susztak, Katalin %A Hamet, Pavel %A Tremblay, Johanne %A de Boer, Ian H %A Böger, Carsten A %A Goessling, Wolfram %A Daniel I Chasman %A Köttgen, Anna %A Kao, W H Linda %A Caroline S Fox %K Chronic disease %K Genome-Wide Association Study %K Genotype %K Humans %X

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

%B Nat Commun %V 7 %P 10023 %8 2016 Jan 21 %G eng %1 http://www.ncbi.nlm.nih.gov/pubmed/26831199?dopt=Abstract %R 10.1038/ncomms10023 %0 Journal Article %J Nat Genet %D 2016 %T Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. %A Okbay, Aysu %A Baselmans, Bart M L %A De Neve, Jan-Emmanuel %A Turley, Patrick %A Nivard, Michel G %A Mark Alan Fontana %A Meddens, S Fleur W %A Richard Karlsson Linnér %A Cornelius A Rietveld %A Derringer, Jaime %A Gratten, Jacob %A Lee, James J %A Liu, Jimmy Z %A de Vlaming, Ronald %A Ahluwalia, Tarunveer S %A Buchwald, Jadwiga %A Cavadino, Alana %A Frazier-Wood, Alexis C %A Furlotte, Nicholas A %A Garfield, Victoria %A Geisel, Marie Henrike %A Gonzalez, Juan R %A Haitjema, Saskia %A Karlsson, Robert %A van der Laan, Sander W %A Ladwig, Karl-Heinz %A J. Lahti %A Sven J van der Lee %A Penelope A Lind %A Tian Liu %A Lindsay K Matteson %A Mihailov, Evelin %A Michael B Miller %A Minica, Camelia C %A Ilja M Nolte %A Dennis O Mook-Kanamori %A van der Most, Peter J %A Christopher J Oldmeadow %A Qian, Yong %A Olli T Raitakari %A Rawal, Rajesh %A Realo, Anu %A Rueedi, Rico %A Schmidt, Börge %A Albert Vernon Smith %A Stergiakouli, Evie %A Toshiko Tanaka %A Kent D Taylor %A Wedenoja, Juho %A Jürgen Wellmann %A Westra, Harm-Jan %A Willems, Sara M %A Wei Zhao %A Amin, Najaf %A Bakshi, Andrew %A Patricia A. Boyle %A Cherney, Samantha %A Cox, Simon R %A Gail Davies %A Davis, Oliver S P %A Ding, Jun %A Nese Direk %A Eibich, Peter %A Emeny, Rebecca T %A Fatemifar, Ghazaleh %A Jessica Faul %A Luigi Ferrucci %A Andreas J Forstner %A Gieger, Christian %A Gupta, Richa %A Tamara B Harris %A Harris, Juliette M %A Holliday, Elizabeth G %A Jouke-Jan Hottenga %A Philip L de Jager %A Marika A Kaakinen %A Kajantie, Eero %A Karhunen, Ville %A Kolcic, Ivana %A Kumari, Meena %A Lenore J Launer %A Lude L Franke %A Li-Gao, Ruifang %A Koini, Marisa %A Loukola, Anu %A Marques-Vidal, Pedro %A Grant W Montgomery %A Mosing, Miriam A %A Paternoster, Lavinia %A Pattie, Alison %A Katja E Petrovic %A Pulkki-Raback, Laura %A Quaye, Lydia %A Katri Räikkönen %A Rudan, Igor %A Rodney J Scott %A Jennifer A Smith %A Angelina R Sutin %A Trzaskowski, Maciej %A Anna A E Vinkhuyzen %A Lei Yu %A Zabaneh, Delilah %A John R. Attia %A David A Bennett %A Klaus Berger %A Bertram, Lars %A Dorret I Boomsma %A Snieder, Harold %A Chang, Shun-Chiao %A Francesco Cucca %A Ian J Deary %A Cornelia M van Duijn %A Johan G Eriksson %A Bültmann, Ute %A Eco J. C. de Geus %A Groenen, Patrick J F %A Gudnason, Vilmundur %A Hansen, Torben %A Catharina A Hartman %A Haworth, Claire M A %A Caroline Hayward %A Andrew C Heath %A Hinds, David A %A Hyppönen, Elina %A Iacono, William G %A Järvelin, Marjo-Riitta %A Jöckel, Karl-Heinz %A Kaprio, Jaakko %A Sharon L R Kardia %A Keltikangas-Järvinen, Liisa %A Kraft, Peter %A Laura D Kubzansky %A Lehtimäki, Terho %A Patrik K E Magnusson %A Nicholas G Martin %A McGue, Matt %A Andres Metspalu %A Melinda C Mills %A de Mutsert, Renée %A Oldehinkel, Albertine J %A Pasterkamp, Gerard %A Nancy L Pedersen %A Plomin, Robert %A Polasek, Ozren %A Power, Christine %A Rich, Stephen S %A Rosendaal, Frits R %A Hester M. den Ruijter %A Schlessinger, David %A Schmidt, Helena %A Svento, Rauli %A Schmidt, Reinhold %A Alizadeh, Behrooz Z %A Thorkild I. A. Sørensen %A Timothy Spector %A Andrew Steptoe %A Antonio Terracciano %A A. Roy Thurik %A Nicholas J Timpson %A Henning Tiemeier %A André G Uitterlinden %A Vollenweider, Peter %A Wagner, Gert G %A David R Weir %A Yang, Jian %A Dalton C Conley %A Hofman, Albert %A Johannesson, Magnus %A David I Laibson %A Sarah E Medland %A Meyer, Michelle N %A Pickrell, Joseph K %A Tõnu Esko %A Krueger, Robert F %A Jonathan P. Beauchamp %A Philipp D Koellinger %A Daniel J. Benjamin %A Bartels, Meike %A Cesarini, David %K Anxiety Disorders %K Bayes Theorem %K depression %K Genome-Wide Association Study %K Humans %K Neuroticism %K Phenotype %K Polymorphism, Single Nucleotide %X

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.

%B Nat Genet %V 48 %P 624-33 %8 2016 06 %G eng %N 6 %1 http://www.ncbi.nlm.nih.gov/pubmed/27089181?dopt=Abstract %R 10.1038/ng.3552 %0 Journal Article %J Nat Genet %D 2016 %T Genome-wide analysis identifies 12 loci influencing human reproductive behavior. %A Nicola Barban %A Jansen, Rick %A de Vlaming, Ronald %A Vaez, Ahmad %A Mandemakers, Jornt J %A Felix C Tropf %A Shen, Xia %A James F Wilson %A Daniel I Chasman %A Ilja M Nolte %A Tragante, Vinicius %A van der Laan, Sander W %A Perry, John R B %A Kong, Augustine %A Ahluwalia, Tarunveer S %A Albrecht, Eva %A Laura M Yerges-Armstrong %A Atzmon, Gil %A Auro, Kirsi %A Kristin L. Ayers %A Bakshi, Andrew %A Ben-Avraham, Danny %A Klaus Berger %A Bergman, Aviv %A Bertram, Lars %A Bielak, Lawrence F %A Bjornsdottir, Gyda %A Bonder, Marc Jan %A Broer, Linda %A Bui, Minh %A Barbieri, Caterina %A Cavadino, Alana %A Chavarro, Jorge E %A Turman, Constance %A Maria Pina Concas %A Cordell, Heather J %A Gail Davies %A Eibich, Peter %A Eriksson, Nicholas %A Tõnu Esko %A Eriksson, Joel %A Falahi, Fahimeh %A Felix, Janine F %A Mark Alan Fontana %A Lude L Franke %A Gandin, Ilaria %A Gaskins, Audrey J %A Gieger, Christian %A Gunderson, Erica P %A Guo, Xiuqing %A Caroline Hayward %A He, Chunyan %A Edith Hofer %A Huang, Hongyan %A Joshi, Peter K %A Kanoni, Stavroula %A Karlsson, Robert %A Kiechl, Stefan %A Kifley, Annette %A Kluttig, Alexander %A Kraft, Peter %A Lagou, Vasiliki %A Lecoeur, Cecile %A Lahti, Jari %A Li-Gao, Ruifang %A Penelope A Lind %A Tian Liu %A Makalic, Enes %A Mamasoula, Crysovalanto %A Lindsay K Matteson %A Mbarek, Hamdi %A McArdle, Patrick F %A McMahon, George %A Meddens, S Fleur W %A Mihailov, Evelin %A Michael B Miller %A Missmer, Stacey A %A Monnereau, Claire %A van der Most, Peter J %A Myhre, Ronny %A Michael A Nalls %A Nutile, Teresa %A Ioanna Panagiota Kalafati %A Porcu, Eleonora %A Prokopenko, Inga %A Rajan, Kumar B %A Rich-Edwards, Janet %A Cornelius A Rietveld %A Robino, Antonietta %A Rose, Lynda M %A Rueedi, Rico %A Ryan, Kathleen A %A Saba, Yasaman %A Schmidt, Daniel %A Jennifer A Smith %A Stolk, Lisette %A Streeten, Elizabeth %A Tönjes, Anke %A Thorleifsson, Gudmar %A Ulivi, Sheila %A Wedenoja, Juho %A Jürgen Wellmann %A Willeit, Peter %A Yao, Jie %A Yengo, Loic %A Jing Hua Zhao %A Wei Zhao %A Zhernakova, Daria V %A Amin, Najaf %A Andrews, Howard %A Balkau, Beverley %A Barzilai, Nir %A Bergmann, Sven %A Biino, Ginevra %A Bisgaard, Hans %A Bønnelykke, Klaus %A Dorret I Boomsma %A Buring, Julie E %A Campbell, Harry %A Cappellani, Stefania %A Ciullo, Marina %A Cox, Simon R %A Francesco Cucca %A Toniolo, Daniela %A Davey-Smith, George %A Ian J Deary %A George Dedoussis %A Deloukas, Panos %A Cornelia M van Duijn %A Eco J. C. de Geus %A Johan G Eriksson %A Jessica Faul %A Cinzia Felicita Sala %A Froguel, Philippe %A Paolo P. Gasparini %A Giorgia G Girotto %A Hans-Jörgen Grabe %A Greiser, Karin Halina %A Groenen, Patrick J F %A de Haan, Hugoline G %A Haerting, Johannes %A Tamara B Harris %A Andrew C Heath %A Heikkilä, Kauko %A Hofman, Albert %A Homuth, Georg %A Holliday, Elizabeth G %A John L Hopper %A Hyppönen, Elina %A Jacobsson, Bo %A Vincent Jaddoe %A Johannesson, Magnus %A Jugessur, Astanand %A Kähönen, Mika %A Kajantie, Eero %A Sharon L R Kardia %A Keavney, Bernard %A Kolcic, Ivana %A Koponen, Päivikki %A Kovacs, Peter %A Kronenberg, Florian %A Kutalik, Zoltán %A La Bianca, Martina %A Lachance, Genevieve %A Iacono, William G %A Lai, Sandra %A Lehtimäki, Terho %A David C Liewald %A Lindgren, Cecilia M %A Yongmei Liu %A Luben, Robert %A Lucht, Michael %A Luoto, Riitta %A Magnus, Per %A Patrik K E Magnusson %A Nicholas G Martin %A McGue, Matt %A McQuillan, Ruth %A Sarah E Medland %A Meisinger, Christa %A Mellström, Dan %A Andres Metspalu %A Traglia, Michela %A Lili Milani %A Mitchell, Paul %A Grant W Montgomery %A Dennis O Mook-Kanamori %A de Mutsert, Renée %A Nohr, Ellen A %A Ohlsson, Claes %A Olsen, Jørn %A Ong, Ken K %A Paternoster, Lavinia %A Pattie, Alison %A Brenda W J H Penninx %A Markus Perola %A Peyser, Patricia A %A Pirastu, Mario %A Polasek, Ozren %A Power, Chris %A Kaprio, Jaakko %A Raffel, Leslie J %A Katri Räikkönen %A Olli T Raitakari %A Ridker, Paul M %A Ring, Susan M %A Roll, Kathryn %A Rudan, Igor %A Ruggiero, Daniela %A Rujescu, Dan %A Veikko Salomaa %A Schlessinger, David %A Schmidt, Helena %A Schmidt, Reinhold %A Schupf, Nicole %A Johannes H Smit %A Sorice, Rossella %A Timothy Spector %A John M Starr %A Stöckl, Doris %A Strauch, Konstantin %A Stumvoll, Michael %A Swertz, Morris A %A Thorsteinsdottir, Unnur %A A. Roy Thurik %A Nicholas J Timpson %A Tung, Joyce Y %A André G Uitterlinden %A Vaccargiu, Simona %A Viikari, Jorma %A Vitart, Veronique %A Völzke, Henry %A Vollenweider, Peter %A Vuckovic, Dragana %A Waage, Johannes %A Wagner, Gert G %A Wang, Jie Jin %A Wareham, Nicholas J %A David R Weir %A Gonneke Willemsen %A Willeit, Johann %A Alan F Wright %A Krina T Zondervan %A Stefansson, Kari %A Krueger, Robert F %A Lee, James J %A Daniel J. Benjamin %A Cesarini, David %A Philipp D Koellinger %A den Hoed, Marcel %A Snieder, Harold %A Melinda C Mills %X

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.

%B Nat Genet %V 48 %P 1462-1472 %8 2016 Dec %G eng %N 12 %1 http://www.ncbi.nlm.nih.gov/pubmed/27798627?dopt=Abstract %R 10.1038/ng.3698 %0 Journal Article %J Depress Anxiety %D 2016 %T GENOME-WIDE ASSOCIATION STUDY (GWAS) AND GENOME-WIDE BY ENVIRONMENT INTERACTION STUDY (GWEIS) OF DEPRESSIVE SYMPTOMS IN AFRICAN AMERICAN AND HISPANIC/LATINA WOMEN. %A Dunn, Erin C %A Wiste, Anna %A Radmanesh, Farid %A Almli, Lynn M %A Gogarten, Stephanie M %A Sofer, Tamar %A Jessica Faul %A Sharon L R Kardia %A Jennifer A Smith %A David R Weir %A Wei Zhao %A Soare, Thomas W %A Saira S Mirza %A Karin Hek %A Henning Tiemeier %A Goveas, Joseph S %A Sarto, Gloria E %A Snively, Beverly M %A Marilyn C Cornelis %A Karestan C Koenen %A Kraft, Peter %A Shaun M Purcell %A Ressler, Kerry J %A Rosand, Jonathan %A Wassertheil-Smoller, Sylvia %A Smoller, Jordan W %K African Americans %K Aged %K depression %K Female %K Gene-Environment Interaction %K Genome-Wide Association Study %K Hispanic Americans %K Humans %K Life Change Events %K Middle Aged %K Phenotype %K Polymorphism, Single Nucleotide %K Risk Factors %K Self Report %X

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'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 × 10(-8) ) and rs75407252 (intronic to CACNA2D3, P = 6.99 × 10(-7) ). In Hispanics/Latinas, the top signals were rs2532087 (located 27 kb from CD38, P = 2.44 × 10(-7) ) and rs4542757 (intronic to DCC, P = 7.31 × 10(-7) ). In the GEWIS with stressful life events, one interaction signal was genome-wide significant in African Americans (rs4652467; P = 4.10 × 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.

%B Depress Anxiety %V 33 %P 265-80 %8 2016 Apr %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/27038408?dopt=Abstract %R 10.1002/da.22484 %0 Journal Article %J Nature %D 2016 %T Genome-wide association study identifies 74 loci associated with educational attainment. %A Okbay, Aysu %A Jonathan P. Beauchamp %A Mark Alan Fontana %A Lee, James J %A Pers, Tune H %A Cornelius A Rietveld %A Turley, Patrick %A Chen, Guo-Bo %A Emilsson, Valur %A Meddens, S Fleur W %A Oskarsson, Sven %A Pickrell, Joseph K %A Thom, Kevin %A Pascal N Timshel %A de Vlaming, Ronald %A Abdel Abdellaoui %A Ahluwalia, Tarunveer S %A Bacelis, Jonas %A Baumbach, Clemens %A Bjornsdottir, Gyda %A Brandsma, Johannes H %A Maria Pina Concas %A Derringer, Jaime %A Furlotte, Nicholas A %A Galesloot, Tessel E %A Giorgia G Girotto %A Gupta, Richa %A Hall, Leanne M %A Sarah E Harris %A Edith Hofer %A Horikoshi, Momoko %A Huffman, Jennifer E %A Kaasik, Kadri %A Ioanna Panagiota Kalafati %A Karlsson, Robert %A Kong, Augustine %A Lahti, Jari %A Sven J van der Lee %A Christiaan de Leeuw %A Penelope A Lind %A Lindgren, Karl-Oskar %A Tian Liu %A Mangino, Massimo %A Marten, Jonathan %A Mihailov, Evelin %A Michael B Miller %A van der Most, Peter J %A Christopher J Oldmeadow %A Payton, Antony %A Pervjakova, Natalia %A Wouter J Peyrot %A Qian, Yong %A Olli T Raitakari %A Rueedi, Rico %A Salvi, Erika %A Schmidt, Börge %A Schraut, Katharina E %A Jianxin Shi %A Albert Vernon Smith %A Poot, Raymond A %A St Pourcain, Beate %A Teumer, Alexander %A Thorleifsson, Gudmar %A Verweij, Niek %A Vuckovic, Dragana %A Jürgen Wellmann %A Westra, Harm-Jan %A Yang, Jingyun %A Wei Zhao %A Zhihong Zhu %A Alizadeh, Behrooz Z %A Amin, Najaf %A Bakshi, Andrew %A Baumeister, Sebastian E %A Biino, Ginevra %A Bønnelykke, Klaus %A Patricia A. Boyle %A Campbell, Harry %A Cappuccio, Francesco P %A Gail Davies %A De Neve, Jan-Emmanuel %A Deloukas, Panos %A Demuth, Ilja %A Ding, Jun %A Eibich, Peter %A Eisele, Lewin %A Eklund, Niina %A Jessica Faul %A Feitosa, Mary F %A Andreas J Forstner %A Gandin, Ilaria %A Gunnarsson, Bjarni %A Halldórsson, Bjarni V %A Tamara B Harris %A Andrew C Heath %A Lynne J Hocking %A Holliday, Elizabeth G %A Homuth, Georg %A Horan, Michael A %A Jouke-Jan Hottenga %A Philip L de Jager %A Joshi, Peter K %A Jugessur, Astanand %A Marika A Kaakinen %A Kähönen, Mika %A Kanoni, Stavroula %A Keltigangas-Järvinen, Liisa %A Lambertus A Kiemeney %A Kolcic, Ivana %A Koskinen, Seppo %A Kraja, Aldi T %A Kroh, Martin %A Kutalik, Zoltán %A Latvala, Antti %A Lenore J Launer %A Lebreton, Maël P %A Douglas F Levinson %A Paul Lichtenstein %A Lichtner, Peter %A David C Liewald %A Loukola, Anu %A Pamela A F Madden %A Mägi, Reedik %A Mäki-Opas, Tomi %A Riccardo E Marioni %A Marques-Vidal, Pedro %A Meddens, Gerardus A %A McMahon, George %A Meisinger, Christa %A Meitinger, Thomas %A Milaneschi, Yusplitri %A Lili Milani %A Grant W Montgomery %A Myhre, Ronny %A Nelson, Christopher P %A Nyholt, Dale R %A William E R Ollier %A Aarno Palotie %A Paternoster, Lavinia %A Nancy L Pedersen %A Katja E Petrovic %A David J Porteous %A Katri Räikkönen %A Ring, Susan M %A Robino, Antonietta %A Rostapshova, Olga %A Rudan, Igor %A Rustichini, Aldo %A Veikko Salomaa %A Sanders, Alan R %A Sarin, Antti-Pekka %A Schmidt, Helena %A Rodney J Scott %A Smith, Blair H %A Jennifer A Smith %A Staessen, Jan A %A Steinhagen-Thiessen, Elisabeth %A Strauch, Konstantin %A Antonio Terracciano %A Tobin, Martin D %A Ulivi, Sheila %A Vaccargiu, Simona %A Quaye, Lydia %A van Rooij, Frank J A %A Venturini, Cristina %A Anna A E Vinkhuyzen %A Völker, Uwe %A Völzke, Henry %A Vonk, Judith M %A Vozzi, Diego %A Waage, Johannes %A Erin B Ware %A Gonneke Willemsen %A John R. Attia %A David A Bennett %A Klaus Berger %A Bertram, Lars %A Bisgaard, Hans %A Dorret I Boomsma %A Ingrid B Borecki %A Bültmann, Ute %A Chabris, Christopher F %A Francesco Cucca %A Cusi, Daniele %A Ian J Deary %A George Dedoussis %A Cornelia M van Duijn %A Johan G Eriksson %A Franke, Barbara %A Lude L Franke %A Paolo P. Gasparini %A Gejman, Pablo V %A Gieger, Christian %A Hans-Jörgen Grabe %A Gratten, Jacob %A Groenen, Patrick J F %A Gudnason, Vilmundur %A van der Harst, Pim %A Caroline Hayward %A Hinds, David A %A Hoffmann, Wolfgang %A Hyppönen, Elina %A Iacono, William G %A Jacobsson, Bo %A Järvelin, Marjo-Riitta %A Jöckel, Karl-Heinz %A Kaprio, Jaakko %A Sharon L R Kardia %A Lehtimäki, Terho %A Lehrer, Steven F %A Patrik K E Magnusson %A Nicholas G Martin %A McGue, Matt %A Andres Metspalu %A Pendleton, Neil %A Brenda W J H Penninx %A Markus Perola %A Nicola Pirastu %A Pirastu, Mario %A Polasek, Ozren %A Posthuma, Danielle %A Power, Christine %A Province, Michael A %A Nilesh J Samani %A Schlessinger, David %A Schmidt, Reinhold %A Thorkild I. A. Sørensen %A Timothy Spector %A Stefansson, Kari %A Thorsteinsdottir, Unnur %A A. Roy Thurik %A Nicholas J Timpson %A Henning Tiemeier %A Tung, Joyce Y %A André G Uitterlinden %A Vitart, Veronique %A Vollenweider, Peter %A David R Weir %A James F Wilson %A Alan F Wright %A Dalton C Conley %A Krueger, Robert F %A George Davey Smith %A Hofman, Albert %A David I Laibson %A Sarah E Medland %A Meyer, Michelle N %A Yang, Jian %A Johannesson, Magnus %A Peter M Visscher %A Tõnu Esko %A Philipp D Koellinger %A Cesarini, David %A Daniel J. Benjamin %K Alzheimer's disease %K Bipolar Disorder %K Cognitive Ability %K Education %K Fetus %K Genome-Wide Association Study %K Humans %K Molecular Sequence Annotation %K Polymorphism, Single Nucleotide %K Schizophrenia %K United Kingdom %X

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.

%B Nature %V 533 %P 539-42 %8 2016 05 26 %G eng %N 7604 %1 http://www.ncbi.nlm.nih.gov/pubmed/27225129?dopt=Abstract %R 10.1038/nature17671 %0 Journal Article %J Aging Cell %D 2016 %T GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium. %A Amy M Matteini %A Toshiko Tanaka %A Karasik, David %A Atzmon, Gil %A Chou, Wen-Chi %A John D Eicher %A Andrew D Johnson %A Alice M. Arnold %A Michele L Callisaya %A Gail Davies %A Daniel S Evans %A Holtfreter, Birte %A Kurt Lohman %A Kathryn L Lunetta %A Mangino, Massimo %A Albert Vernon Smith %A Jennifer A Smith %A Teumer, Alexander %A Lei Yu %A Dan E Arking %A Aron S Buchman %A Chibinik, Lori B %A Philip L de Jager %A Jessica Faul %A Melissa E Garcia %A Gillham-Nasenya, Irina %A Gudnason, Vilmundur %A Hofman, Albert %A Hsu, Yi-Hsiang %A Ittermann, Till %A Lahousse, Lies %A David C Liewald %A Yongmei Liu %A Lopez, Lorna %A Fernando Rivadeneira %A Rotter, Jerome I %A Siggeirsdottir, Kristin %A John M Starr %A Thomson, Russell %A Tranah, Gregory J %A André G Uitterlinden %A Völker, Uwe %A Völzke, Henry %A David R Weir %A Kristine Yaffe %A Wei Zhao %A Wei Vivian Zhuang %A Zmuda, Joseph M %A David A Bennett %A Steven R Cummings %A Ian J Deary %A Luigi Ferrucci %A Tamara B Harris %A Sharon L R Kardia %A Kocher, Thomas %A Stephen B Kritchevsky %A Psaty, Bruce M %A Seshadri, Sudha %A Timothy Spector %A Velandai K Srikanth %A Beverly G Windham %A Zillikens, M Carola %A Anne B Newman %A Jeremy D Walston %A Douglas P Kiel %A Joanne M Murabito %K Adult %K Aged %K Chromatin Immunoprecipitation %K Cohort Studies %K Epigenesis, Genetic %K Genome-Wide Association Study %K Hand Strength %K Humans %K Molecular Sequence Annotation %K Muscle Strength %K Polymorphism, Single Nucleotide %K Quantitative Trait Loci %K Reproducibility of Results %X

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 × 10(-8) ) and 39 suggestive (P-value< 5 × 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 × 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.

%B Aging Cell %V 15 %P 792-800 %8 2016 10 %G eng %N 5 %1 http://www.ncbi.nlm.nih.gov/pubmed/27325353?dopt=Abstract %R 10.1111/acel.12468 %0 Journal Article %J Mol Psychiatry %D 2015 %T Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53949). %A Gail Davies %A Armstrong, N. %A Joshua C. Bis %A Bressler, J. %A Chouraki, V. %A Giddaluru, S. %A Edith Hofer %A Carla A Ibrahim-Verbaas %A Kirin, M. %A J. Lahti %A Sven J van der Lee %A Stephanie Le Hellard %A Tian Liu %A Riccardo E Marioni %A Christopher J Oldmeadow %A Postmus, I. %A Albert Vernon Smith %K Aged %K Aged, 80 and over %K Atherosclerosis %K Cognition %K Cognition Disorders %K Cohort Studies %K Female %K Genetic Predisposition to Disease %K Genome-Wide Association Study %K HMGN1 Protein %K Humans %K Male %K Middle Aged %K Neuropsychological tests %K Phenotype %K Polymorphism, Single Nucleotide %K Scotland %X

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53,949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10(-9), MIR2113; rs17522122, P=2.55 × 10(-8), AKAP6; rs10119, P=5.67 × 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.

%B Mol Psychiatry %I 20 %V 20 %P 183-92 %8 2015 Feb %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/25644384?dopt=Abstract %2 PMC4356746 %4 genetics/genetics/GENOME-WIDE ASSOCIATION/TOMM40/ABCG1/MEF2C/complex train anaysis/Atherosclerosis Risk in Communities Study/cross-national study %$ 999999 %R 10.1038/mp.2014.188 %0 Journal Article %J Nature %D 2015 %T Genetic studies of body mass index yield new insights for obesity biology. %A Locke, Adam E %A Kahali, Bratati %A Berndt, Sonja I %A Justice, Anne E %A Pers, Tune H %A Day, Felix R %A Powell, Corey %A Vedantam, Sailaja %A Buchkovich, Martin L %A Yang, Jian %A Croteau-Chonka, Damien C %A Tõnu Esko %A Fall, Tove %A Ferreira, Teresa %A Gustafsson, Stefan %A Kutalik, Zoltán %A Luan, Jian'an %A Mägi, Reedik %A Randall, Joshua C %A Thomas W Winkler %A Andrew R Wood %A Workalemahu, Tsegaselassie %A Jessica Faul %A Jennifer A Smith %A Jing Hua Zhao %A Wei Zhao %A Chen, Jin %A Rudolf Ferhmann %A Hedman, Åsa K %A Karjalainen, Juha %A Schmidt, Ellen M %A Absher, Devin %A Amin, Najaf %A Anderson, Denise %A Beekman, Marian %A Bolton, Jennifer L %A Bragg-Gresham, Jennifer L %A Buyske, Steven %A Demirkan, Ayse %A Deng, Guohong %A Georg B Ehret %A Feenstra, Bjarke %A Feitosa, Mary F %A Fischer, Krista %A Goel, Anuj %A Gong, Jian %A Jackson, Anne U %A Kanoni, Stavroula %A Kleber, Marcus E %A Kristiansson, Kati %A Lim, Unhee %A Lotay, Vaneet %A Mangino, Massimo %A Irene Mateo Leach %A Medina-Gomez, Carolina %A Sarah E Medland %A Michael A Nalls %A Palmer, Cameron D %A Pasko, Dorota %A Pechlivanis, Sonali %A Peters, Marjolein J %A Prokopenko, Inga %A Shungin, Dmitry %A Stančáková, Alena %A Strawbridge, Rona J %A Yun Ju Sung %A Toshiko Tanaka %A Teumer, Alexander %A Trompet, Stella %A van der Laan, Sander W %A van Setten, Jessica %A Jana V. van Vliet-Ostaptchouk %A Wang, Zhaoming %A Yengo, Loic %A Zhang, Weihua %A Isaacs, Aaron %A Albrecht, Eva %A Ärnlöv, Johan %A Arscott, Gillian M %A Attwood, Antony P %A Bandinelli, Stefania %A Barrett, Amy %A Bas, Isabelita N %A Bellis, Claire %A Bennett, Amanda J %A Berne, Christian %A Blagieva, Roza %A Blüher, Matthias %A Böhringer, Stefan %A Bonnycastle, Lori L %A Böttcher, Yvonne %A Boyd, Heather A %A Bruinenberg, Marcel %A Caspersen, Ida H %A Yii-Der I Chen %A Robert Clark %A Daw, E Warwick %A de Craen, Anton J M %A Delgado, Graciela %A Dimitriou, Maria %A Doney, Alex S F %A Eklund, Niina %A Estrada, Karol %A Eury, Elodie %A Folkersen, Lasse %A Fraser, Ross M %A Melissa E Garcia %A Geller, Frank %A Giedraitis, Vilmantas %A Gigante, Bruna %A Alan S Go %A Golay, Alain %A Goodall, Alison H %A Gordon, Scott D %A Gorski, Mathias %A Hans-Jörgen Grabe %A Grallert, Harald %A Grammer, Tanja B %A Gräßler, Jürgen %A Grönberg, Henrik %A Groves, Christopher J %A Gusto, Gaëlle %A Jeffrey Haessler %A Hall, Per %A Haller, Toomas %A Hallmans, Göran %A Catharina A Hartman %A Hassinen, Maija %A Caroline Hayward %A Heard-Costa, Nancy L %A Helmer, Quinta %A Hengstenberg, Christian %A Oddgeir L Holmen %A Jouke-Jan Hottenga %A James, Alan L %A Janina Jeff %A Johansson, Åsa %A Jolley, Jennifer %A Juliusdottir, Thorhildur %A Kinnunen, Leena %A Koenig, Wolfgang %A Koskenvuo, Markku %A Kratzer, Wolfgang %A Laitinen, Jaana %A Lamina, Claudia %A Leander, Karin %A Lee, Nanette R %A Lichtner, Peter %A Lars Lind %A Lindström, Jaana %A Ken Sin Lo %A Lobbens, Stéphane %A Lorbeer, Roberto %A Lu, Yingchang %A Mach, François %A Patrik K E Magnusson %A Mahajan, Anubha %A McArdle, Wendy L %A McLachlan, Stela %A Menni, Cristina %A Merger, Sigrun %A Mihailov, Evelin %A Lili Milani %A Moayyeri, Alireza %A Monda, Keri L %A Morken, Mario A %A Mulas, Antonella %A Müller, Gabriele %A Müller-Nurasyid, Martina %A Musk, Arthur W %A Nagaraja, Ramaiah %A Markus M Nöthen %A Ilja M Nolte %A Pilz, Stefan %A Nigel W Rayner %A Renstrom, Frida %A Rettig, Rainer %A Ried, Janina S %A Ripke, Stephan %A Neil R Robertson %A Rose, Lynda M %A Sanna, Serena %A Scharnagl, Hubert %A Scholtens, Salome %A Schumacher, Fredrick R %A Scott, William R %A Seufferlein, Thomas %A Jianxin Shi %A Albert Vernon Smith %A Smolonska, Joanna %A Stanton, Alice V %A Steinthorsdottir, Valgerdur %A Kathleen E Stirrups %A Heather M Stringham %A Sundström, Johan %A Swertz, Morris A %A Swift, Amy J %A Syvänen, Ann-Christine %A Tan, Sian-Tsung %A Bamidele O Tayo %A Thorand, Barbara %A Thorleifsson, Gudmar %A Tyrer, Jonathan P %A Uh, Hae-Won %A Vandenput, Liesbeth %A Verhulst, Frank C %A Vermeulen, Sita H %A Verweij, Niek %A Vonk, Judith M %A Lindsay L Waite %A Warren, Helen R %A Dawn M Waterworth %A Michael N Weedon %A Wilkens, Lynne R %A Willenborg, Christina %A Wilsgaard, Tom %A Wojczynski, Mary K %A Wong, Andrew %A Alan F Wright %A Zhang, Qunyuan %A Brennan, Eoin P %A Murim Choi %A Dastani, Zari %A Alexander W Drong %A Eriksson, Per %A Franco-Cereceda, Anders %A Gådin, Jesper R %A Gharavi, Ali G %A Goddard, Michael E %A Handsaker, Robert E %A Huang, Jinyan %A Karpe, Fredrik %A Kathiresan, Sekar %A Keildson, Sarah %A Kiryluk, Krzysztof %A Kubo, Michiaki %A Lee, Jong-Young %A Liang, Liming %A Lifton, Richard P %A Ma, Baoshan %A McCarroll, Steven A %A McKnight, Amy J %A Min, Josine L %A Moffatt, Miriam F %A Grant W Montgomery %A Joanne M Murabito %A Nicholson, George %A Nyholt, Dale R %A Okada, Yukinori %A Perry, John R B %A Dorajoo, Rajkumar %A Reinmaa, Eva %A Salem, Rany M %A Sandholm, Niina %A Scott, Robert A %A Stolk, Lisette %A Takahashi, Atsushi %A Tanaka, Toshihiro %A Ferdinand M van 't Hooft %A Anna A E Vinkhuyzen %A Westra, Harm-Jan %A Wei Zhang %A Krina T Zondervan %A Andrew C Heath %A Arveiler, Dominique %A Bakker, Stephan J L %A Beilby, John %A Bergman, Richard N %A Blangero, John %A Bovet, Pascal %A Campbell, Harry %A Caulfield, Mark J %A Cesana, Giancarlo %A Chakravarti, Aravinda %A Daniel I Chasman %A Chines, Peter S %A Collins, Francis S %A Crawford, Dana C %A Cupples, L Adrienne %A Cusi, Daniele %A Danesh, John %A de Faire, Ulf %A Hester M den Ruijter %A Dominiczak, Anna F %A Erbel, Raimund %A Erdmann, Jeanette %A Johan G Eriksson %A Farrall, Martin %A Felix, Stephan B %A Ferrannini, Ele %A Ferrières, Jean %A Ford, Ian %A Forouhi, Nita G %A Forrester, Terrence %A Franco, Oscar H %A Gansevoort, Ron T %A Gejman, Pablo V %A Gieger, Christian %A Gottesman, Omri %A Gudnason, Vilmundur %A Gyllensten, Ulf %A Hall, Alistair S %A Tamara B Harris %A Andrew T Hattersley %A Hicks, Andrew A %A Hindorff, Lucia A %A Aroon Hingorani %A Hofman, Albert %A Homuth, Georg %A Hovingh, G Kees %A Humphries, Steve E %A Hunt, Steven C %A Hyppönen, Elina %A Illig, Thomas %A Jacobs, Kevin B %A Järvelin, Marjo-Riitta %A Jöckel, Karl-Heinz %A Johansen, Berit %A Jousilahti, Pekka %A Jukema, J Wouter %A Jula, Antti M %A Kaprio, Jaakko %A Kastelein, John J P %A Keinanen-Kiukaanniemi, Sirkka M %A Lambertus A Kiemeney %A Knekt, Paul %A Kooner, Jaspal S %A Charles Kooperberg %A Kovacs, Peter %A Kraja, Aldi T %A Kumari, Meena %A Kuusisto, Johanna %A Lakka, Timo A %A Langenberg, Claudia %A Loic Le Marchand %A Lehtimäki, Terho %A Lyssenko, Valeriya %A Männistö, Satu %A Marette, André %A Matise, Tara C %A McKenzie, Colin A %A McKnight, Barbara %A Moll, Frans L %A Morris, Andrew D %A Morris, Andrew P %A Murray, Jeffrey C %A Nelis, Mari %A Ohlsson, Claes %A Oldehinkel, Albertine J %A Ong, Ken K %A Pamela A F Madden %A Pasterkamp, Gerard %A Peden, John F %A Peters, Annette %A Postma, Dirkje S %A Pramstaller, Peter P %A Price, Jackie F %A Qi, Lu %A Olli T Raitakari %A Rankinen, Tuomo %A Rao, D C %A Rice, Treva K %A Ridker, Paul M %A Rioux, John D %A Ritchie, Marylyn D %A Rudan, Igor %A Veikko Salomaa %A Nilesh J Samani %A Saramies, Jouko %A Sarzynski, Mark A %A Schunkert, Heribert %A Schwarz, Peter E H %A Peter Sever %A Alan R Shuldiner %A Sinisalo, Juha %A Stolk, Ronald P %A Strauch, Konstantin %A Tönjes, Anke %A Trégouët, David-Alexandre %A Tremblay, Angelo %A Tremoli, Elena %A Virtamo, Jarmo %A Vohl, Marie-Claude %A Völker, Uwe %A Waeber, Gérard %A Gonneke Willemsen %A Witteman, Jacqueline C %A Zillikens, M Carola %A Adair, Linda S %A Amouyel, Philippe %A Asselbergs, Folkert W %A Assimes, Themistocles L %A Bochud, Murielle %A Boehm, Bernhard O %A Boerwinkle, Eric %A Bornstein, Stefan R %A Erwin P Bottinger %A Bouchard, Claude %A Cauchi, Stéphane %A Chambers, John C %A Chanock, Stephen J %A Cooper, Richard S %A de Bakker, Paul I W %A George Dedoussis %A Luigi Ferrucci %A Franks, Paul W %A Froguel, Philippe %A Leif C Groop %A Christopher A Haiman %A Hamsten, Anders %A Hui, Jennie %A Hunter, David J %A Hveem, Kristian %A Kaplan, Robert C %A Mika Kivimäki %A Kuh, Diana %A Laakso, Markku %A Yongmei Liu %A Nicholas G Martin %A März, Winfried %A Melbye, Mads %A Andres Metspalu %A Moebus, Susanne %A Munroe, Patricia B %A Njølstad, Inger %A Ben A Oostra %A Palmer, Colin N A %A Nancy L Pedersen %A Markus Perola %A Pérusse, Louis %A Peters, Ulrike %A Power, Chris %A Quertermous, Thomas %A Rauramaa, Rainer %A Fernando Rivadeneira %A Saaristo, Timo E %A Saleheen, Danish %A Sattar, Naveed %A Eric E Schadt %A Schlessinger, David %A Eline P Slagboom %A Snieder, Harold %A Timothy Spector %A Thorsteinsdottir, Unnur %A Stumvoll, Michael %A Tuomilehto, Jaakko %A André G Uitterlinden %A Uusitupa, Matti %A van der Harst, Pim %A Walker, Mark %A Wallaschofski, Henri %A Wareham, Nicholas J %A Watkins, Hugh %A David R Weir %A Wichmann, H-Erich %A James F Wilson %A Zanen, Pieter %A Ingrid B Borecki %A Deloukas, Panos %A Caroline S Fox %A Iris M Heid %A Jeff O'Connell %A David P Strachan %A Stefansson, Kari %A Cornelia M van Duijn %A Gonçalo R Abecasis %A Lude L Franke %A Timothy M Frayling %A McCarthy, Mark I %A Peter M Visscher %A Scherag, Andre %A Willer, Cristen J %A Boehnke, Michael %A Mohlke, Karen L %A Lindgren, Cecilia M %A Beckmann, Jacques S %A Barroso, Inês %A Kari E North %A Ingelsson, Erik %A Joel N Hirschhron %A Ruth J F Loos %A Elizabeth K Speliotes %K Age Factors %K BMI %K Continental Population Groups %K Energy Metabolism %K Europe %K Female %K Genome-Wide Association Study %K Glutamic Acid %K Humans %K Insulin %K Male %K Obesity %K Polymorphism, Single Nucleotide %K Quantitative Trait Loci %K Synapses %X

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 × 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.

%B Nature %V 518 %P 197-206 %8 2015 Feb 12 %G eng %N 7538 %1 http://www.ncbi.nlm.nih.gov/pubmed/25673413?dopt=Abstract %R 10.1038/nature14177 %0 Journal Article %J Soc Sci Med %D 2015 %T Genetic vulnerability to diabetes and obesity: does education offset the risk? %A Sze Y Liu %A Stefan Walter %A Jessica R Marden %A David Rehkopf %A Laura D Kubzansky %A Thu T Nguyen %A M. Maria Glymour %K Aged %K Body Mass Index %K Diabetes Mellitus, Type 2 %K Educational Status %K European Continental Ancestry Group %K Female %K Genetic Predisposition to Disease %K Genotype %K Glycated Hemoglobin A %K Health Status Disparities %K Humans %K Male %K Middle Aged %K Obesity %K Risk Factors %K Social determinants of health %X

The prevalence of type 2 diabetes (T2D) and obesity has recently increased dramatically. These common diseases are likely to arise from the interaction of multiple genetic, socio-demographic and environmental risk factors. While previous research has found genetic risk and education to be strong predictors of these diseases, few studies to date have examined their joint effects. This study investigates whether education modifies the association between genetic background and risk for type 2 diabetes (T2D) and obesity. Using data from non-Hispanic Whites in the Health and Retirement Study (HRS, n = 8398), we tested whether education modifies genetic risk for obesity and T2D, offsetting genetic effects; whether this effect is larger for individuals who have high risk for other (unobserved) reasons, i.e., at higher quantiles of HbA1c and BMI; and whether effects differ by gender. We measured T2D risk using Hemoglobin A1c (HbA1c) level, and obesity risk using body-mass index (BMI). We constructed separate genetic risk scores (GRS) for obesity and diabetes respectively based on the most current available information on the single nucleotide polymorphism (SNPs) confirmed as genome-wide significant predictors for BMI (29 SNPs) and diabetes risk (39 SNPs). Linear regression models with years of schooling indicate that the effect of genetic risk on HbA1c is smaller among people with more years of schooling and larger among those with less than a high school (HS) degree compared to HS degree-holders. Quantile regression models show that the GRS × education effect systematically increased along the HbA1c outcome distribution; for example the GRS × years of education interaction coefficient was -0.01 (95% CI = -0.03, 0.00) at the 10th percentile compared to -0.03 (95% CI = -0.07, 0.00) at the 90th percentile. These results suggest that education may be an important socioeconomic source of heterogeneity in responses to genetic vulnerability to T2D.

%B Soc Sci Med %V 127 %P 150-8 %8 2015 Feb %G eng %U http://www.sciencedirect.com/science/article/pii/S0277953614005760 %1 http://www.ncbi.nlm.nih.gov/pubmed/25245452?dopt=Abstract %R 10.1016/j.socscimed.2014.09.009 %0 Journal Article %J Alzheimers Dement %D 2015 %T Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples: Mendelian randomization analyses. %A Mukherjee, Shubhabrata %A Stefan Walter %A Kauwe, John S K %A Andrew J Saykin %A David A Bennett %A Eric B Larson %A Paul K Crane %A M. Maria Glymour %K Aged %K Aged, 80 and over %K Alzheimer disease %K Body Mass Index %K Female %K Genotype %K Humans %K Linear Models %K Male %K Mendelian Randomization Analysis %K Obesity %K Phenotype %K Polymorphism, Single Nucleotide %K Risk Factors %X

Observational research shows that higher body mass index (BMI) increases Alzheimer's disease (AD) risk, but it is unclear whether this association is causal. We applied genetic variants that predict BMI in Mendelian randomization analyses, an approach that is not biased by reverse causation or confounding, to evaluate whether higher BMI increases AD risk. We evaluated individual-level data from the AD Genetics Consortium (ADGC: 10,079 AD cases and 9613 controls), the Health and Retirement Study (HRS: 8403 participants with algorithm-predicted dementia status), and published associations from the Genetic and Environmental Risk for AD consortium (GERAD1: 3177 AD cases and 7277 controls). No evidence from individual single-nucleotide polymorphisms or polygenic scores indicated BMI increased AD risk. Mendelian randomization effect estimates per BMI point (95% confidence intervals) were as follows: ADGC, odds ratio (OR) = 0.95 (0.90-1.01); HRS, OR = 1.00 (0.75-1.32); GERAD1, OR = 0.96 (0.87-1.07). One subscore (cellular processes not otherwise specified) unexpectedly predicted lower AD risk.

%B Alzheimers Dement %V 11 %P 1439-1451 %8 2015 Dec %G eng %N 12 %1 http://www.ncbi.nlm.nih.gov/pubmed/26079416?dopt=Abstract %R 10.1016/j.jalz.2015.05.015 %0 Report %D 2015 %T The Great Recession, Retirement and Related Outcomes %A Alan L Gustman %A Thomas L. Steinmeier %A N. Tabatabai %K Employment and Labor Force %K Expectations %K Public Policy %X This paper uses data from the Health and Retirement Study to examine retirement and related labor market outcomes for the Early Boomer cohort, those in their mid-fifties at the onset of the Great Recession. Outcomes are then compared with older cohorts at the same age. The Great Recession increased their probability of being laid off and the length of time it took to find other full-time employment. Differences in layoffs between those affected by the recession and members of older cohorts in turn accounted for almost the entire difference between cohorts in employment change with age. The Great Recession does not appear, however, to have depressed the wages in subsequent jobs for those who experienced a layoff. In 2010, 17 percent of the Early Boomers were Not Working and Not Retired or Partially Retired, and 6 percent were unemployed, leaving at least 9 percent who were not working and not unemployed but not retired or only partially retired. At the recession s peak, half of those who experienced a layoff ended up in the Not Retired or Partially Retired, Not Working category. But only a quarter of those who declared themselves to be Not Retired or Partially Retired, and were Not Working, had experienced a layoff. Most of the jump in Not Retired or Partially Retired, Not Working appears to reflect a change in expectations about the potential or need for future work, a change that is not the result of an actual job loss. %I Cambridge, MA, National Bureau of Economic Research %G eng %4 great Recession/labor Force Participation/Unemployment/expectations %$ 999999 %0 Journal Article %J J Gerontol A Biol Sci Med Sci %D 2015 %T GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy. %A Broer, Linda %A Aron S Buchman %A Deelen, Joris %A Daniel S Evans %A Jessica Faul %A Kathryn L Lunetta %A Sebastiani, Paola %A Jennifer A Smith %A Albert Vernon Smith %A Toshiko Tanaka %A Lei Yu %A Alice M. Arnold %A Aspelund, Thor %A Emelia J Benjamin %A Philip L de Jager %A Guðny Eiríksdóttir %A Melissa E Garcia %A Hofman, Albert %A Kaplan, Robert C %A Sharon L R Kardia %A Douglas P Kiel %A Ben A Oostra %A Orwoll, Eric S %A Parimi, Neeta %A Psaty, Bruce M %A Fernando Rivadeneira %A Rotter, Jerome I %A Seshadri, Sudha %A Andrew B Singleton %A Henning Tiemeier %A André G Uitterlinden %A Wei Zhao %A Bandinelli, Stefania %A David A Bennett %A Luigi Ferrucci %A Gudnason, Vilmundur %A Tamara B Harris %A Karasik, David %A Lenore J Launer %A Thomas T Perls %A Eline P Slagboom %A Tranah, Gregory J %A David R Weir %A Anne B Newman %A Cornelia M van Duijn %A Joanne M Murabito %K Aged %K Aged, 80 and over %K Apolipoproteins E %K Cell Adhesion Molecules %K Cohort Studies %K Female %K Forkhead Box Protein O3 %K Forkhead Transcription Factors %K Genome-Wide Association Study %K Humans %K Longevity %K Male %K Middle Aged %K Polymorphism, Single Nucleotide %K Receptors, Kainic Acid %X

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 × 10(-7)) and GRIK2 (odds ratio = 1.24; p value = 5.09 × 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 = 1.85×10(-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.

%B J Gerontol A Biol Sci Med Sci %V 70 %P 110-8 %8 2015 Jan %G eng %U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296168/ %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/25199915?dopt=Abstract %R 10.1093/gerona/glu166 %0 Journal Article %J BMC Genet %D 2014 %T Genetic diversity is a predictor of mortality in humans. %A Bihlmeyer, Nathan A %A Brody, Jennifer A %A Albert Vernon Smith %A Kathryn L Lunetta %A Michael A Nalls %A Jennifer A Smith %A Toshiko Tanaka %A Gail Davies %A Lei Yu %A Saira S Mirza %A Teumer, Alexander %A Coresh, Josef %A Pankow, James S %A Franceschini, Nora %A Scaria, Anish %A Oshima, Junko %A Psaty, Bruce M %A Gudnason, Vilmundur %A Guðny Eiríksdóttir %A Tamara B Harris %A Li, Hanyue %A Karasik, David %A Douglas P Kiel %A Melissa E Garcia %A Yongmei Liu %A Jessica Faul %A Sharon L R Kardia %A Wei Zhao %A Luigi Ferrucci %A Allerhand, Michael %A David C Liewald %A Redmond, Paul %A John M Starr %A Philip L de Jager %A Nese Direk %A Mohammed Arfan Ikram %A André G Uitterlinden %A Homuth, Georg %A Lorbeer, Roberto %A Hans-Jörgen Grabe %A Lenore J Launer %A Joanne M Murabito %A Andrew B Singleton %A David R Weir %A Bandinelli, Stefania %A Ian J Deary %A David A Bennett %A Henning Tiemeier %A Kocher, Thomas %A Lumley, Thomas %A Dan E Arking %K Genome-Wide Association Study %K Heterozygote %K Humans %K Mortality %K Polymorphism, Single Nucleotide %K Proportional Hazards Models %X

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'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.

%B BMC Genet %V 15 %P 159 %8 2014 Dec 29 %G eng %U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4301661/ %1 http://www.ncbi.nlm.nih.gov/pubmed/25543667?dopt=Abstract %R 10.1186/s12863-014-0159-7 %0 Journal Article %J PLoS One %D 2014 %T Genomic assortative mating in marriages in the United States. %A Guo, Guang %A Wang, Lin %A Hexuan Liu %A Randall, Thomas %K Data collection %K Female %K Genome, Human %K Genomics %K Genotype %K Humans %K Male %K Marriage %K Middle Aged %K Phenotype %K Polymorphism, Single Nucleotide %K Reproduction %K United States %X

Assortative mating in phenotype in human marriages has been widely observed. Using genome-wide genotype data from the Framingham Heart study (FHS; number of married couples = 989) and Health Retirement Survey (HRS; number of married couples = 3,474), this study investigates genomic assortative mating in human marriages. Two types of genomic marital correlations are calculated. The first is a correlation specific to a single married couple "averaged" over all available autosomal single-nucleotide polymorphism (SNPs). In FHS, the average married-couple correlation is 0.0018 with p = 3 × 10(-5); in HRS, it is 0.0017 with p = 7.13 × 10(-13). The marital correlation among the positively assorting SNPs is 0.001 (p = .0043) in FHS and 0.015 (p = 1.66 × 10(-24)) in HRS. The sizes of these estimates in FHS and HRS are consistent with what are suggested by the distribution of the allelic combination. The study also estimated SNP-specific correlation "averaged" over all married couples. Suggestive evidence is reported. Future studies need to consider a more general form of genomic assortment, in which different allelic forms in homologous genes and non-homologous genes result in the same phenotype.

%B PLoS One %V 9 %P e112322 %8 2014 %G eng %N 11 %1 http://www.ncbi.nlm.nih.gov/pubmed/25384046?dopt=Abstract %R 10.1371/journal.pone.0112322 %0 Report %D 2014 %T The Great Recession, Decline and Rebound in Household Wealth for the Near Retirement Population %A Alan L Gustman %A Thomas L. Steinmeier %A N. Tabatabai %K Health Conditions and Status %K Net Worth and Assets %K Public Policy %X This paper uses data from the Health and Retirement Study to examine the effects of the Great Recession on the wealth held by the near retirement age population from 2006 to 2012. For the Early Boomer cohort (ages 51 to 56 in 2004), real wealth in 2012 remained 3.6 percent below its 2006 value. This is a modest decline considering the fall in asset values during the Great Recession. Much of the decline in wealth over the 2006 to 2010 period was cushioned by wealth originating from Social Security and defined benefit pensions. For the most part, these are stable sums that ensured a major fraction of total wealth did not decline as a result of the recession. The rebound in asset values observed between 2010 and 2012 mitigated, but did not erase, the asset losses experienced in the first years of the Great Recession. Effects of the Great Recession varied with the household's initial wealth. Those who were in the highest wealth deciles typically had a larger share of their assets subject to the influence of declining markets, and were hurt most severely. Unlike those falling in lower wealth deciles, they have yet to regain all the wealth they lost during the recession. Recovering losses in assets is only part of the story. The assets held by members of the cohort nearing retirement at the onset of the recession would normally have grown over ensuing years. Members of older HRS cohorts accumulated assets rapidly in the years just before retirement. Those on the cusp of retiring at the onset of the recession would be much better off had they had enjoyed similar growth in assets as experienced by members of older cohorts. The bottom line is that the losses in assets imposed by the Great Recession were relatively modest. The recovery has helped. But much of the remaining penalty due to the Great Recession is in the failure of assets to grow beyond their initial levels. %I Cambridge, MA, National Bureau of Economic Research %G eng %4 great Recession/Asset accumulation/household wealth/asset values/loss recovery %$ 999999 %0 Journal Article %J Am J Epidemiol %D 2013 %T A Genetic IV Analysis to Assess the Effect of Body Mass Index on Depression in the Health And Retirement Study %A Stefan Walter %A Mejía-Guevara, Iván %A Eric J. Tchetgen Tchetgen %A Karestan C Koenen %A Ichiro Kawachi %A Laura D Kubzansky %A M. Maria Glymour %K Genetics %K Health Conditions and Status %K Public Policy %X Background: The relationship between adiposity and mental health remains controversial despite extensive prior observational research. We use a genetic risk score (GRS) as an instrumental variable (IV) to estimate effects of increases in body mass index (BMI) on depressive symptoms. Methods: Data are from 11842 (whites = 10322, blacks = 1520) individuals from the nationally representative Health and Retirement Study with data on a 10-item Center for Epidemiologic Studies Depression (CESD) scale and genetics collected in 2006 or 2008. Based on 32 Single Nucleotide Polymorphisms (SNPs) known to predict BMI, we calculated a GRS as the sum of the number of risk alleles multiplied by the per allele effect size on BMI (based on prior publica- tions). We conducted over-identification tests with 4 IVs using subsets of the SNPs organized based on biological pathways (adiposity, appetite, and cardio-pulmonary factors) by which the genes might influence adiposity. Self-reported BMI prior to the assessment of CESD was used for validation of the external instrument. The CESD score was regressed on each genetic IV plus population stratification eigenvectors to derive the IV effect estimate. We compared these to conventional effect estimates derived from regressing CESD on self-reported BMI. Results: The GRS significantly predicted BMI in blacks (r2=0.016, p 0.001) and whites (r2=0.010, p 0.001). Self-reported BMI significantly predicted CESD, more strongly in whites (0.043, 95 -CI: 0.036, 0.05) than blacks (0.021, CI: 0.004, 0.038). IV effect estimates were large and statistically significant for whites (0.0 96, CI: 0.026, 0.167) but had very wide CIs for blacks (0.016, CI: -0.224, 0.256) . Over-identification tests showed no evidence of possible pleiotropy in the genetic risk score. Conclusions: Our IV analysis reveals that genotypes associated with BMI are also associated with depressive symptoms in whites, supporting a causal effect of BMI on depression. %B Am J Epidemiol %I 177 %V 177 %P S12 %G eng %4 public Health/occupational health/Body Mass Index/Genetic Markers/risk alleles/genetic risk score/Depression/biological pathways/mental Health/genetics/genetics %$ 69334 %0 Journal Article %J Am J Hum Genet %D 2013 %T Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations. %A Franceschini, Nora %A Fox, Ervin %A Zhang, Zhaogong %A Edwards, Todd L %A Michael A Nalls %A Yun Ju Sung %A Bamidele O Tayo %A Yan V Sun %A Gottesman, Omri %A Adebawole Adeyemo %A Andrew D Johnson %A Young, J Hunter %A Kenneth Rice %A Duan, Qing %A Chen, Fang %A Yun Li %A Tang, Hua %A Myriam Fornage %A Keene, Keith L %A Andrews, Jeanette S %A Jennifer A Smith %A Jessica Faul %A Guangfa, Zhang %A Guo, Wei %A Liu, Yu %A Murray, Sarah S %A Musani, Solomon K %A Srinivasan, Sathanur %A Digna R Velez Edwards %A Wang, Heming %A Becker, Lewis C %A Bovet, Pascal %A Bochud, Murielle %A Broeckel, Ulrich %A Burnier, Michel %A Carty, Cara %A Daniel I Chasman %A Georg B Ehret %A Chen, Wei-Min %A Chen, Guanjie %A Wei Chen %A Ding, Jingzhong %A Dreisbach, Albert W %A Michele K Evans %A Guo, Xiuqing %A Melissa E Garcia %A Jensen, Rich %A Keller, Margaux F %A Lettre, Guillaume %A Lotay, Vaneet %A Martin, Lisa W %A Moore, Jason H %A Alanna C Morrison %A Thomas H Mosley %A Ogunniyi, Adesola %A Walter R Palmas %A George J Papanicolaou %A Alan Penman %A Polak, Joseph F %A Ridker, Paul M %A Babatunde Salako %A Andrew B Singleton %A Daniel Shriner %A Kent D Taylor %A Ramachandran S Vasan %A Kerri Wiggins %A Williams, Scott M %A Yanek, Lisa R %A Wei Zhao %A Alan B Zonderman %A Becker, Diane M %A Berenson, Gerald %A Boerwinkle, Eric %A Erwin P Bottinger %A Cushman, Mary %A Charles B Eaton %A Nyberg, Fredrik %A Gerardo Heiss %A Joel N Hirschhron %A Howard, Virginia J %A Karczewsk, Konrad J %A Lanktree, Matthew B %A Liu, Kiang %A Yongmei Liu %A Ruth J F Loos %A Margolis, Karen %A Snyder, Michael %A Psaty, Bruce M %A Schork, Nicholas J %A David R Weir %A Charles N Rotimi %A Sale, Michele M %A Tamara B Harris %A Sharon L R Kardia %A Hunt, Steven C %A Donna K Arnett %A Redline, Susan %A Cooper, Richard S %A Neil Risch %A Rao, D C %A Rotter, Jerome I %A Chakravarti, Aravinda %A Reiner, Alex P %A Levy, Daniel %A Keating, Brendan J %A Zhu, Xiaofeng %K Africa %K African Continental Ancestry Group %K Blood pressure %K Cohort Studies %K Databases, Genetic %K Genetic Loci %K Genetic Predisposition to Disease %K Genome-Wide Association Study %K Humans %K Polymorphism, Single Nucleotide %K Quantitative Trait, Heritable %K Reproducibility of Results %X

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 × 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.

%B Am J Hum Genet %V 93 %P 545-54 %8 2013 Sep 05 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/23972371?dopt=Abstract %R 10.1016/j.ajhg.2013.07.010 %0 Journal Article %J Science %D 2013 %T GWAS of 126,559 individuals identifies genetic variants associated with educational attainment. %A Cornelius A Rietveld %A Sarah E Medland %A Derringer, Jaime %A Yang, Jian %A Tõnu Esko %A Martin, Nicolas W %A Westra, Harm-Jan %A Shakhbazov, Konstantin %A Abdel Abdellaoui %A Agrawal, Arpana %A Albrecht, Eva %A Alizadeh, Behrooz Z %A Amin, Najaf %A Barnard, John %A Baumeister, Sebastian E %A Benke, Kelly S %A Bielak, Lawrence F %A Boatman, Jeffrey A %A Patricia A. Boyle %A Gail Davies %A Christiaan de Leeuw %A Eklund, Niina %A Daniel S Evans %A Rudolf Ferhmann %A Fischer, Krista %A Gieger, Christian %A Gjessing, Håkon K %A Hägg, Sara %A Harris, Jennifer R %A Caroline Hayward %A Holzapfel, Christina %A Carla A Ibrahim-Verbaas %A Ingelsson, Erik %A Jacobsson, Bo %A Joshi, Peter K %A Jugessur, Astanand %A Marika A Kaakinen %A Kanoni, Stavroula %A Karjalainen, Juha %A Kolcic, Ivana %A Kristiansson, Kati %A Kutalik, Zoltán %A J. Lahti %A Lee, Sang H %A Lin, Peng %A Penelope A Lind %A Yongmei Liu %A Kurt Lohman %A Loitfelder, Marisa %A McMahon, George %A Vidal, Pedro Marques %A Osorio Meirelles %A Lili Milani %A Myhre, Ronny %A Nuotio, Marja-Liisa %A Christopher J Oldmeadow %A Katja E Petrovic %A Wouter J Peyrot %A Polasek, Ozren %A Quaye, Lydia %A Reinmaa, Eva %A Rice, John P %A Rizzi, Thais S %A Schmidt, Helena %A Schmidt, Reinhold %A Albert Vernon Smith %A Jennifer A Smith %A Toshiko Tanaka %A Antonio Terracciano %A van der Loos, Matthijs J H M %A Vitart, Veronique %A Völzke, Henry %A Jürgen Wellmann %A Lei Yu %A Wei Zhao %A Allik, Jüri %A John R. Attia %A Bandinelli, Stefania %A Bastardot, François %A Jonathan P. Beauchamp %A David A Bennett %A Klaus Berger %A Laura Bierut %A Dorret I Boomsma %A Bültmann, Ute %A Campbell, Harry %A Chabris, Christopher F %A Cherkas, Lynn %A Chung, Mina K %A Francesco Cucca %A de Andrade, Mariza %A Philip L de Jager %A De Neve, Jan-Emmanuel %A Ian J Deary %A George Dedoussis %A Deloukas, Panos %A Dimitriou, Maria %A Guðny Eiríksdóttir %A Elderson, Martin F %A Johan G Eriksson %A Jessica Faul %A Luigi Ferrucci %A Melissa E Garcia %A Grönberg, Henrik %A Guðnason, Vilmundur %A Hall, Per %A Harris, Juliette M %A Tamara B Harris %A Nicholas D Hastie %A Andrew C Heath %A Dena G Hernandez %A Hoffmann, Wolfgang %A Hofman, Adriaan %A Holle, Rolf %A Holliday, Elizabeth G %A Jouke-Jan Hottenga %A Iacono, William G %A Illig, Thomas %A Järvelin, Marjo-Riitta %A Kähönen, Mika %A Kaprio, Jaakko %A Kirkpatrick, Robert M %A Kowgier, Matthew %A Latvala, Antti %A Lenore J Launer %A Lawlor, Debbie A %A Lehtimäki, Terho %A Li, Jingmei %A Paul Lichtenstein %A Lichtner, Peter %A David C Liewald %A Pamela A F Madden %A Patrik K E Magnusson %A Mäkinen, Tomi E %A Masala, Marco %A McGue, Matt %A Andres Metspalu %A Mielck, Andreas %A Michael B Miller %A Grant W Montgomery %A Mukherjee, Sutapa %A Nyholt, Dale R %A Ben A Oostra %A Palmer, Lyle J %A Aarno Palotie %A Brenda W J H Penninx %A Markus Perola %A Peyser, Patricia A %A Preisig, Martin %A Katri Räikkönen %A Olli T Raitakari %A Realo, Anu %A Ring, Susan M %A Ripatti, Samuli %A Fernando Rivadeneira %A Rudan, Igor %A Rustichini, Aldo %A Veikko Salomaa %A Sarin, Antti-Pekka %A Schlessinger, David %A Rodney J Scott %A Snieder, Harold %A St Pourcain, Beate %A John M Starr %A Sul, Jae Hoon %A Surakka, Ida %A Svento, Rauli %A Teumer, Alexander %A Henning Tiemeier %A van Rooij, Frank J A %A Van Wagoner, David R %A Vartiainen, Erkki %A Viikari, Jorma %A Vollenweider, Peter %A Vonk, Judith M %A Waeber, Gérard %A David R Weir %A Wichmann, H-Erich %A Elisabeth Widen %A Gonneke Willemsen %A James F Wilson %A Alan F Wright %A Dalton C Conley %A Davey-Smith, George %A Lude L Franke %A Groenen, Patrick J F %A Hofman, Albert %A Johannesson, Magnus %A Sharon L R Kardia %A Krueger, Robert F %A David I Laibson %A Nicholas G Martin %A Meyer, Michelle N %A Posthuma, Danielle %A A. Roy Thurik %A Nicholas J Timpson %A André G Uitterlinden %A Cornelia M van Duijn %A Peter M Visscher %A Daniel J. Benjamin %A Cesarini, David %A Philipp D Koellinger %K Cognition %K Educational Status %K Endophenotypes %K Female %K Genetic Loci %K Genome-Wide Association Study %K Humans %K Male %K Multifactorial Inheritance %K Polymorphism, Single Nucleotide %X

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.

%B Science %V 340 %P 1467-71 %8 2013 Jun 21 %G eng %N 6139 %1 http://www.ncbi.nlm.nih.gov/pubmed/23722424?dopt=Abstract %R 10.1126/science.1235488 %0 Journal Article %J Soc Secur Bull %D 2012 %T The growth in Social Security benefits among the retirement-age population from increases in the cap on covered earnings. %A Alan L Gustman %A Thomas L. Steinmeier %A N. Tabatabai %K Aged %K Cohort Studies %K Female %K Humans %K Insurance Benefits %K Male %K Middle Aged %K Models, Econometric %K Public Policy %K Salaries and Fringe Benefits %K Social Security %K Taxes %K United States %X

Analysts have proposed raising the maximum level of earnings subject to the Social Security payroll tax (the "tax max") to improve long-term Social Security Trust Fund solvency. This article investigates how raising the tax max leads to the "leakage" of portions of the additional revenue into higher benefit payments. Using Health and Retirement Study data matched to Social Security earnings records, we compare historical payroll tax payments and benefit amounts for Early Boomers (born 1948-1953) with tax and benefit simulations had they been subject to the tax max (adjusted for wage growth) faced by cohorts 12 and 24 years older. We find that 43.2 percent of the additional payroll tax revenue attributable to tax max increases affecting Early Boomers relative to taxes paid by the cohort 12 years older leaked into higher benefits. For Early Boomers relative to those 24 years older, we find 53.5 percent leakage.

%B Soc Secur Bull %I 72 %V 72 %P 49-61 %8 2012 %G eng %U https://www.ssa.gov/policy/docs/ssb/v72n2/v72n2p49.html %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/22799138?dopt=Abstract %4 Social security/payroll tax/Public policy/retirement planning/taxation %$ 69572 %0 Report %D 2010 %T The Growth in Social Security Benefits Among the Retirement Age Population from Increases in the Cap on Covered Earnings %A Alan L Gustman %A Thomas L. Steinmeier %A Tabatabai, Nahid %K Demographics %K Public Policy %K Social Security %X This paper investigates how increases in the level of maximum earnings subject to the Social Security payroll tax have affected Social Security benefits and taxes. The analysis uses data from the Health and Retirement Study to ask how different the present value of own benefits and taxes would be for the cohort born from 1948 to 1953 (ages 51 to 56 in 2004) if they faced the lower cap on the payroll tax that faced those born 12 and 24 years earlier, but otherwise had the same earnings stream and faced the same benefit formula. We find that for those in the Early Boomer cohort of the Health and Retirement Study, ages 51 to 56 in 2004, that after adjusting for nominal wage growth, benefits were increased by 1.5 percent by the increase in the payroll tax ceiling compared to the cohort 12 years older, and by 3.7 percent over the benefits under the payroll tax ceiling for the cohort 24 years older. Tax receipts were increased by 5.3 and 10.6 percent over tax receipts that would have been collected under the tax ceilings that applied to the cohorts 12 and 24 years older respectively. About 22 percent of the additional tax revenues created by the increase in the payroll tax cap between the Early Boomer cohort and those 12 years older led to increased benefits. Similarly, about 27 percent of the additional tax revenues created by the increase in the payroll tax cap between the Early Boomer cohort and those 24 years older led to increase benefits. Results are also presented separately for men and women, for those in the top quartile of earners, and for those at the tax ceiling throughout their work lives. %B NBER Working Paper %I National Bureau of Economic Research %C Cambridge, MA %G eng %4 social Security/early boomers/earnings and Benefits File/Public Policy/payroll tax/tax revenues %$ 24370 %R 10.3386/w16501