TY - JOUR T1 - Gender and the Subjective Well-Being of Older Widows and Widowers. JF - The International Journal of Aging and Human Development Y1 - 2023 A1 - Geng, Jing A1 - Calasanti, Toni M KW - gender repertoires KW - Happiness KW - inequalities KW - Life Satisfaction AB -

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.

ER - TY - JOUR T1 - Gender of study partners and research participants associated with differences in study partner ratings of cognition and activity level. JF - J Gerontol B Psychol Sci Soc Sci Y1 - 2023 A1 - Stites, Shana D A1 - Gurian, Anna A1 - Coykendall, Cameron A1 - Largent, Emily A A1 - Harkins, Kristin A1 - Karlawish, Jason A1 - Coe, Norma B KW - activity level KW - Cognition KW - gender AB -

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.

ER - TY - JOUR T1 - A genome-wide association study of frailty identifies significant genetic correlation with neuropsychiatric, cardiovascular, and inflammation pathways. JF - Geroscience Y1 - 2023 A1 - Ye, Yixuan A1 - Noche, Rommell B A1 - Szejko, Natalia A1 - Both, Cameron P A1 - Acosta, Julian N A1 - Leasure, Audrey C A1 - Brown, Stacy C A1 - Sheth, Kevin N A1 - Gill, Thomas M A1 - Zhao, Hongyu A1 - Falcone, Guido J KW - genome-wide. cardiovascular KW - Inflammation KW - neuropsychiatric AB -

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.

ER - TY - JOUR T1 - Gender, Age of Migration, and Cognitive Life Expectancies among Older Latinos: Evidence from the Health and Retirement Study. JF - The Journals of Gerontology, Series B Y1 - 2022 A1 - Garcia, Marc A A1 - Tarraf, Wassim A1 - Reyes, Adriana M A1 - Chiu, Chi-Tsun KW - cognitive aging KW - Migration and the Life-course KW - race and ethnicity AB -

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.

VL - 77 IS - 12 ER - TY - RPRT T1 - The Gender Gap in Household Bargaining Power: A Revealed-Preference Approach Y1 - 2022 A1 - Ran Gu A1 - Cameron Peng A1 - Weilong Zhang KW - gender gap AB - 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 CY - Paris, France UR - https://www.weilongzhang.com/uploads/1/2/3/7/123776250/intrahh_v17.pdf ER - TY - JOUR T1 - Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning. JF - Molecular Psychiatry Y1 - 2022 A1 - Lahti, Jari A1 - Tuominen, Samuli A1 - Yang, Qiong A1 - Pergola, Giulio A1 - Ahmad, Shahzad A1 - Amin, Najaf A1 - Armstrong, Nicola J A1 - Beiser, Alexa A1 - Bey, Katharina A1 - Bis, Joshua C A1 - Boerwinkle, Eric A1 - Bressler, Jan A1 - Campbell, Archie A1 - Campbell, Harry A1 - Chen, Qiang A1 - Corley, Janie A1 - Cox, Simon R A1 - Davies, Gail A1 - De Jager, Philip L A1 - Derks, Eske M A1 - Jessica Faul A1 - Fitzpatrick, Annette L A1 - Fohner, Alison E A1 - Ford, Ian A1 - Fornage, Myriam A1 - Gerring, Zachary A1 - Grabe, Hans J A1 - Grodstein, Francine A1 - Gudnason, Vilmundur A1 - Simonsick, Eleanor A1 - Holliday, Elizabeth G A1 - Joshi, Peter K A1 - Kajantie, Eero A1 - Kaprio, Jaakko A1 - Karell, Pauliina A1 - Kleineidam, Luca A1 - Knol, Maria J A1 - Kochan, Nicole A A1 - Kwok, John B A1 - Leber, Markus A1 - Lam, Max A1 - Lee, Teresa A1 - Li, Shuo A1 - Loukola, Anu A1 - Luck, Tobias A1 - Marioni, Riccardo E A1 - Mather, Karen A A1 - Medland, Sarah A1 - Mirza, Saira S A1 - Nalls, Mike A A1 - Nho, Kwangsik A1 - O'Donnell, Adrienne A1 - Oldmeadow, Christopher A1 - Painter, Jodie A1 - Pattie, Alison A1 - Reppermund, Simone A1 - Risacher, Shannon L A1 - Rose, Richard J A1 - Sadashivaiah, Vijay A1 - Scholz, Markus A1 - Satizabal, Claudia L A1 - Schofield, Peter W A1 - Schraut, Katharina E A1 - Scott, Rodney J A1 - Simino, Jeannette A1 - Smith, Albert V A1 - Smith, Jennifer A A1 - Stott, David J A1 - Surakka, Ida A1 - Teumer, Alexander A1 - Thalamuthu, Anbupalam A1 - Trompet, Stella A1 - Turner, Stephen T A1 - van der Lee, Sven J A1 - Villringer, Arno A1 - Völker, Uwe A1 - Wilson, Robert S A1 - Wittfeld, Katharina A1 - Vuoksimaa, Eero A1 - Xia, Rui A1 - Yaffe, Kristine A1 - Yu, Lei A1 - Zare, Habil A1 - Zhao, Wei A1 - Ames, David A1 - Attia, John A1 - Bennett, David A A1 - Brodaty, Henry A1 - Chasman, Daniel I A1 - Goldman, Aaron L A1 - Hayward, Caroline A1 - Ikram, M Arfan A1 - Jukema, J Wouter A1 - Sharon L R Kardia A1 - Lencz, Todd A1 - Loeffler, Markus A1 - Mattay, Venkata S A1 - Palotie, Aarno A1 - Psaty, Bruce M A1 - Ramirez, Alfredo A1 - Ridker, Paul M A1 - Riedel-Heller, Steffi G A1 - Sachdev, Perminder S A1 - Saykin, Andrew J A1 - Scherer, Martin A1 - Schofield, Peter R A1 - Sidney, Stephen A1 - Starr, John M A1 - Trollor, Julian A1 - Ulrich, William A1 - Wagner, Michael A1 - David R Weir A1 - Wilson, James F A1 - Wright, Margaret J A1 - Weinberger, Daniel R A1 - Debette, Stéphanie A1 - Eriksson, Johan G A1 - Mosley, Thomas H A1 - Launer, Lenore J A1 - van Duijn, Cornelia M A1 - Deary, Ian J A1 - Seshadri, Sudha A1 - Räikkönen, Katri KW - Genome KW - health outcomes KW - Memory KW - neurocognitive outcomes KW - polygenic score KW - Verbal Learning AB -

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.

ER - TY - JOUR T1 - Gateway to Global Aging Data: Resources for Cross-National Comparisons of Family, Social Environment, and Healthy Aging. JF - The Journals of Gerontology: Series B Y1 - 2021 A1 - Lee, Jinkook A1 - Drystan F. Phillips A1 - Wilkens, Jenny KW - Cross-Country KW - Gateway to Global Aging KW - social network AB -

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.

VL - 76 IS - Supplement_1 ER - TY - Generic T1 - The Gender Gap in Household Bargaining Power: A Portfolio-Choice Approach Y1 - 2021 A1 - Ran Gu A1 - Cameron Peng A1 - Weilong Zhang KW - gender gap AB - 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. PB - SSRN CY - Paris, France ER - TY - JOUR T1 - Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci. JF - Mol Psychiatry Y1 - 2021 A1 - de Las Fuentes, Lisa A1 - Yun Ju Sung A1 - Noordam, Raymond A1 - Thomas W Winkler A1 - Feitosa, Mary F A1 - Schwander, Karen A1 - Bentley, Amy R A1 - Brown, Michael R A1 - Guo, Xiuqing A1 - Alisa Manning A1 - Daniel I Chasman A1 - Aschard, Hugues A1 - Traci M Bartz A1 - Bielak, Lawrence F A1 - Campbell, Archie A1 - Cheng, Ching-Yu A1 - Dorajoo, Rajkumar A1 - Hartwig, Fernando P A1 - Horimoto, A R V R A1 - Li, Changwei A1 - Li-Gao, Ruifang A1 - Liu, Yongmei A1 - Marten, Jonathan A1 - Musani, Solomon K A1 - Ntalla, Ioanna A1 - Rankinen, Tuomo A1 - Melissa Richard A1 - Sim, Xueling A1 - Smith, Albert V A1 - Tajuddin, Salman M A1 - Bamidele O Tayo A1 - Vojinovic, Dina A1 - Warren, Helen R A1 - Xuan, Deng A1 - Alver, Maris A1 - Boissel, Mathilde A1 - Jin-Fang Chai A1 - Chen, Xu A1 - Christensen, Kaare A1 - Divers, Jasmin A1 - Evangelou, Evangelos A1 - Gao, Chuan A1 - Giorgia G Girotto A1 - Sarah E Harris A1 - He, Meian A1 - Hsu, Fang-Chi A1 - Kühnel, Brigitte A1 - Laguzzi, Federica A1 - Li, Xiaoyin A1 - Lyytikäinen, Leo-Pekka A1 - Ilja M Nolte A1 - Poveda, Alaitz A1 - Rauramaa, Rainer A1 - Riaz, Muhammad A1 - Rueedi, Rico A1 - Shu, Xiao-Ou A1 - Snieder, Harold A1 - Sofer, Tamar A1 - Takeuchi, Fumihiko A1 - Verweij, Niek A1 - Erin B Ware A1 - Weiss, Stefan A1 - Yanek, Lisa R A1 - Amin, Najaf A1 - Dan E Arking A1 - Donna K Arnett A1 - Bergmann, Sven A1 - Boerwinkle, Eric A1 - Brody, Jennifer A A1 - Broeckel, Ulrich A1 - Brumat, Marco A1 - Burke, Gregory A1 - Cabrera, Claudia P A1 - Canouil, Mickaël A1 - Chee, Miao Li A1 - Chen, Yii-Der Ida A1 - Cocca, Massimiliano A1 - Connell, John A1 - de Silva, H Janaka A1 - de Vries, Paul S A1 - Eiriksdottir, Gudny A1 - Jessica Faul A1 - Fisher, Virginia A1 - Forrester, Terrence A1 - Fox, Ervin F A1 - Friedlander, Yechiel A1 - Gao, He A1 - Gigante, Bruna A1 - Giulianini, Franco A1 - Gu, Chi Charles A1 - Gu, Dongfeng A1 - Tamara B Harris A1 - He, Jiang A1 - Heikkinen, Sami A1 - Heng, Chew-Kiat A1 - Hunt, Steven A1 - Ikram, M Arfan A1 - Irvin, Marguerite R A1 - Kähönen, Mika A1 - Kavousi, Maryam A1 - Khor, Chiea Chuen A1 - Kilpeläinen, Tuomas O A1 - Koh, Woon-Puay A1 - Komulainen, Pirjo A1 - Kraja, Aldi T A1 - Krieger, J E A1 - Langefeld, Carl D A1 - Li, Yize A1 - Liang, Jingjing A1 - David C Liewald A1 - Liu, Ching-Ti A1 - Liu, Jianjun A1 - Kurt Lohman A1 - Mägi, Reedik A1 - McKenzie, Colin A A1 - Meitinger, Thomas A1 - Andres Metspalu A1 - Milaneschi, Yuri A1 - Lili Milani A1 - Dennis O Mook-Kanamori A1 - Michael A Nalls A1 - Nelson, Christopher P A1 - Norris, Jill M A1 - Jeff O'Connell A1 - Ogunniyi, Adesola A1 - Padmanabhan, Sandosh A1 - Palmer, Nicholette D A1 - Nancy L Pedersen A1 - Thomas T Perls A1 - Peters, Annette A1 - Petersmann, Astrid A1 - Peyser, Patricia A A1 - Polasek, Ozren A1 - David J Porteous A1 - Raffel, Leslie J A1 - Rice, Treva K A1 - Rotter, Jerome I A1 - Rudan, Igor A1 - Rueda-Ochoa, Oscar-Leonel A1 - Sabanayagam, Charumathi A1 - Babatunde Salako A1 - Schreiner, Pamela J A1 - Shikany, James M A1 - Stephen Sidney A1 - Sims, Mario A1 - Sitlani, Colleen M A1 - Smith, Jennifer A A1 - John M Starr A1 - Strauch, Konstantin A1 - Swertz, Morris A A1 - Teumer, Alexander A1 - Tham, Yih Chung A1 - André G Uitterlinden A1 - Vaidya, Dhananjay A1 - van der Ende, M Yldau A1 - Waldenberger, Melanie A1 - Wang, Lihua A1 - Wang, Ya-Xing A1 - Wei, Wen-Bin A1 - David R Weir A1 - Wen, Wanqing A1 - Yao, Jie A1 - Yu, Bing A1 - Yu, Caizheng A1 - Yuan, Jian-Min A1 - Zhao, Wei A1 - Alan B Zonderman A1 - Becker, Diane M A1 - Bowden, Donald W A1 - Ian J Deary A1 - Dörr, Marcus A1 - Tõnu Esko A1 - Freedman, Barry I A1 - Froguel, Philippe A1 - Paolo P. Gasparini A1 - Gieger, Christian A1 - Jost Bruno Jonas A1 - Kammerer, Candace M A1 - Kato, Norihiro A1 - Lakka, Timo A A1 - Leander, Karin A1 - Lehtimäki, Terho A1 - Patrik K E Magnusson A1 - Marques-Vidal, Pedro A1 - Brenda W J H Penninx A1 - Nilesh J Samani A1 - van der Harst, Pim A1 - Wagenknecht, Lynne E A1 - Wu, Tangchun A1 - Zheng, Wei A1 - Zhu, Xiaofeng A1 - Bouchard, Claude A1 - Cooper, Richard S A1 - Correa, Adolfo A1 - Michele K Evans A1 - Gudnason, Vilmundur A1 - Caroline Hayward A1 - Horta, Bernardo L A1 - Tanika N Kelly A1 - Stephen B Kritchevsky A1 - Levy, Daniel A1 - Walter R Palmas A1 - Pereira, A C A1 - Province, Michael M A1 - Psaty, Bruce M A1 - Ridker, Paul M A1 - Charles N Rotimi A1 - Tai, E Shyong A1 - van Dam, Rob M A1 - Cornelia M van Duijn A1 - Wong, Tien Yin A1 - Kenneth Rice A1 - Gauderman, W James A1 - Alanna C Morrison A1 - Kari E North A1 - Sharon L R Kardia A1 - Caulfield, Mark J A1 - Elliott, Paul A1 - Munroe, Patricia B A1 - Franks, Paul W A1 - Rao, Dabeeru C A1 - Myriam Fornage KW - Blood pressure KW - Epistasis, Genetic KW - Genetic Loci KW - Genome-Wide Association Study KW - Humans KW - Hypertension KW - Polymorphism, Single Nucleotide AB -

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.

VL - 26 IS - 6 ER - TY - JOUR T1 - Geriatric Syndromes and Atrial Fibrillation: Prevalence and Association with Anticoagulant Use in a National Cohort of Older Americans. JF - Journal of the American Geriatrics Society Y1 - 2021 A1 - Sachin J Shah A1 - Margaret C Fang A1 - Sun Y Jeon A1 - Gregorich, Steven E A1 - Kenneth E Covinsky KW - anticoagulants KW - Atrial Fibrillation KW - Epidemiology KW - geriatric syndromes AB -

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.

VL - 69 IS - 2 ER - TY - JOUR T1 - Genome-wide association study of cognitive function in diverse Hispanics/Latinos: results from the Hispanic Community Health Study/Study of Latinos. JF - Translational Psychiatry Y1 - 2020 A1 - Jian, Xueqiu A1 - Sofer, Tamar A1 - Wassim Tarraf A1 - Bressler, Jan A1 - Jessica Faul A1 - Zhao, Wei A1 - Scott M Ratliff A1 - Lamar, Melissa A1 - Lenore J Launer A1 - Laurie, Cathy C A1 - Schneiderman, Neil A1 - David R Weir A1 - Wright, Clinton B A1 - Kristine Yaffe A1 - Zeng, Donglin A1 - DeCarli, Charles A1 - Thomas H Mosley A1 - Smith, Jennifer A A1 - Hector M González A1 - Myriam Fornage KW - Aged KW - Cognition KW - Genome-Wide Association Study KW - Hispanic or Latino KW - Humans KW - Middle Aged KW - Neuropsychological tests KW - Public Health KW - Ubiquitin-Conjugating Enzymes AB -

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.

VL - 10 IS - 1 ER - TY - JOUR T1 - Glycosylated Hemoglobin Level, Race/Ethnicity, and Cognition in Midlife and Early Old Age JF - Research in Human Development Y1 - 2020 A1 - Ortiz, Kasim A1 - Marc Garcia A1 - Emily Briceño A1 - Diminich, Erica D. A1 - Arévalo, Sandra P. A1 - Vega, Irving E. A1 - Wassim Tarraf KW - biomarker data KW - cognitive function KW - Racial/ethnic differences AB - 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. VL - 17 SN - 1542-7609 IS - 1 ER - TY - JOUR T1 - Glycated hemoglobin and all-cause and cause-specific mortality among adults with and without diabetes. JF - Journal of Clinical Endocrinology and Metabolism Y1 - 2019 A1 - Li, Fu-Rong A1 - Zhang, Xi-Ru A1 - Zhong, Wen-Fang A1 - Li, Zhi-Hao A1 - Gao, Xiang A1 - Virginia Byers Kraus A1 - Lv, Yue-Bin A1 - Zou, Meng-Chen A1 - Chen, Guo-Chong A1 - Chen, Pei-Liang A1 - Zhang, Min-Yi A1 - Kur, Akech Kuol Akech A1 - Shi, Xiao-Ming A1 - Wu, Xian-Bo A1 - Mao, Chen KW - Biomarkers KW - Diabetes KW - Mortality AB -

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.

U1 - http://www.ncbi.nlm.nih.gov/pubmed/30896760?dopt=Abstract ER - TY - JOUR T1 - The growing American health penalty: International trends in the employment of older workers with poor health JF - Social Science Research Y1 - 2019 A1 - Ben Baumberg Geiger A1 - René Böheim A1 - Thomas Leoni KW - Disability KW - Employment KW - health KW - Panel data KW - Social Security KW - Welfare AB - 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. VL - 82 UR - http://www.sciencedirect.com/science/article/pii/S0049089X1830560X ER - TY - JOUR T1 - Gender, Spousal Caregiving, and Depression: Does Paid Work Matter? JF - Journal of Marriage and Family Y1 - 2018 A1 - Glauber, Rebecca A1 - Day, Melissa D. KW - Caregiving KW - Depressive symptoms KW - Gender Differences KW - Purpose in life KW - Social Support AB - 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. VL - 80 IS - 2 JO - Fam Relat ER - TY - JOUR T1 - Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence JF - Nature Genetics Y1 - 2018 A1 - Savage, Jeanne E. A1 - Philip R Jansen A1 - Stringer, Sven A1 - Watanabe, Kyoko A1 - Bryois, Julien A1 - Christiaan de Leeuw A1 - Nagel, Mats A1 - Awasthi, Swapnil A1 - Barr, Peter B. A1 - Coleman, Jonathan R. I. A1 - Grasby, Katrina L. A1 - Anke R Hammerschlag A1 - Kaminski, Jakob A. A1 - Karlsson, Robert A1 - Krapohl, Eva A1 - Lam, Max A1 - Nygaard, Marianne A1 - Chandra A Reynolds A1 - Joey W Trampush A1 - Young, Hannah A1 - Zabaneh, Delilah A1 - Hägg, Sara A1 - Narelle K Hansell A1 - Ida Karlsson A1 - Linnarsson, Sten A1 - Grant W Montgomery A1 - Muñoz-Manchado, Ana B. A1 - Quinlan, Erin B. A1 - Schumann, Gunter A1 - Skene, Nathan G. A1 - Webb, Bradley T. A1 - White, Tonya A1 - Dan E Arking A1 - Avramopoulos, Dimitrios A1 - Robert M Bilder A1 - Bitsios, Panos A1 - Katherine E Burdick A1 - Tyrone D. Cannon A1 - Chiba-Falek, Ornit A1 - Christoforou, Andrea A1 - Elizabeth T. Cirulli A1 - Congdon, Eliza A1 - Corvin, Aiden A1 - Gail Davies A1 - Ian J Deary A1 - DeRosse, Pamela A1 - Dickinson, Dwight A1 - Djurovic, Srdjan A1 - Donohoe, Gary A1 - Conley, Emily Drabant A1 - Johan G Eriksson A1 - Espeseth, Thomas A1 - Nelson A. Freimer A1 - Giakoumaki, Stella A1 - Giegling, Ina A1 - Gill, Michael A1 - David C. Glahn A1 - Ahmad R Hariri A1 - Hatzimanolis, Alex A1 - Matthew C Keller A1 - Knowles, Emma A1 - Koltai, Deborah A1 - Konte, Bettina A1 - Lahti, Jari A1 - Stephanie Le Hellard A1 - Lencz, Todd A1 - David C Liewald A1 - London, Edythe A1 - Astri J Lundervold A1 - Anil K. Malhotra A1 - Melle, Ingrid A1 - Morris, Derek A1 - Anna C Need A1 - William E R Ollier A1 - Aarno Palotie A1 - Payton, Antony A1 - Pendleton, Neil A1 - Russell A Poldrack A1 - Katri Räikkönen A1 - Reinvang, Ivar A1 - Roussos, Panos A1 - Rujescu, Dan A1 - Fred W Sabb A1 - Matthew A Scult A1 - Smeland, Olav B. A1 - Smyrnis, Nikolaos A1 - John M Starr A1 - Vidar M Steen A1 - Nikos C Stefanis A1 - Richard E Straub A1 - Sundet, Kjetil A1 - Henning Tiemeier A1 - Aristotle N Voineskos A1 - Daniel R Weinberger A1 - Elisabeth Widen A1 - Yu, Jin A1 - Gonçalo R Abecasis A1 - Andreassen, Ole A. A1 - Breen, Gerome A1 - Christiansen, Lene A1 - Debrabant, Birgit A1 - Danielle M. Dick A1 - Heinz, Andreas A1 - Hjerling-Leffler, Jens A1 - Mohammed Arfan Ikram A1 - Kendler, Kenneth S. A1 - Nicholas G Martin A1 - Sarah E Medland A1 - Nancy L Pedersen A1 - Plomin, Robert A1 - Tinca J Polderman A1 - Ripke, Stephan A1 - van der Sluis, Sophie A1 - Patrick F. Sullivan A1 - Scott Vrieze A1 - Margaret J Wright A1 - Posthuma, Danielle KW - Genome-Wide Association Study KW - Intelligence KW - Meta-analyses AB - 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. VL - 50 UR - 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 IS - 7 JO - Nat Genet ER - TY - JOUR T1 - A genome-wide association study for extremely high intelligence JF - Molecular Psychiatry Y1 - 2018 A1 - Zabaneh, D A1 - Krapohl, E A1 - Gaspar, H A A1 - Curtis, C A1 - Lee, S H A1 - Patel, H A1 - Newhouse, S A1 - Wu, H M A1 - Simpson, M A A1 - Putallaz, M A1 - Lubinski, D A1 - Plomin, R A1 - Breen, G KW - Cognitive Ability KW - Education KW - Genome KW - Hereditary KW - Humans AB - 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. VL - 23 UR - http://www.nature.com/doifinder/10.1038/mp.2017.121http://www.nature.com/doifinder/10.1038/mp.2017.121 IS - 5 JO - Mol Psychiatry ER - TY - JOUR T1 - Gender Differences in Spousal Care Across the Later Life Course. JF - Res Aging Y1 - 2017 A1 - Glauber, Rebecca KW - Activities of Daily Living KW - Aged KW - Caregivers KW - Cross-Sectional Studies KW - Employment KW - Female KW - Home Care Services KW - Humans KW - Male KW - Marriage KW - Middle Aged KW - Sex Factors KW - Spouses AB -

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.

VL - 39 UR - http://www.ncbi.nlm.nih.gov/pubmed/27193046 IS - 8 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27193046?dopt=Abstract ER - TY - JOUR T1 - Gene-by-Psychosocial Factor Interactions Influence Diastolic Blood Pressure in European and African Ancestry Populations: Meta-Analysis of Four Cohort Studies. JF - Int J Environ Res Public Health Y1 - 2017 A1 - Wei Zhao A1 - Yasutake, Kalyn A1 - August, Carmella A1 - Scott M Ratliff A1 - Jessica Faul A1 - Boerwinkle, Eric A1 - Chakravarti, Aravinda A1 - Ana V. Diez-Roux A1 - Gao, Yan A1 - Michael E Griswold A1 - Gerardo Heiss A1 - Sharon L R Kardia A1 - Alanna C Morrison A1 - Musani, Solomon K A1 - Mwasongwe, Stanford A1 - Kari E North A1 - Rose, Kathryn M A1 - Sims, Mario A1 - Yan V Sun A1 - David R Weir A1 - Belinda L Needham KW - Blood pressure KW - Genetics KW - GWAS KW - Meta-analyses KW - Psychosocial KW - Socioeconomic factors AB - 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. VL - 14 IS - 12 U1 - http://www.ncbi.nlm.nih.gov/pubmed/29258278?dopt=Abstract ER - TY - JOUR T1 - Genetic architecture of epigenetic and neuronal ageing rates in human brain regions JF - Nature Communications Y1 - 2017 A1 - Lu, Ake T A1 - Hannon, Eilis A1 - Morgan E. Levine A1 - Eileen M. Crimmins A1 - Lunnon, Katie A1 - Mill, Jonathan A1 - Daniel H. Geschwind A1 - Horvath, Steve KW - Genetics AB - 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 ). VL - 8 UR - http://www.nature.com/doifinder/10.1038/ncomms15353http://www.nature.com/doifinder/10.1038/ncomms15353 JO - Nat Comms ER - TY - JOUR T1 - Genetic variants specific to aging-related verbal memory: Insights from GWASs in a population-based cohort. JF - PLoS One Y1 - 2017 A1 - Thalida E. Arpawong A1 - Pendleton, Neil A1 - Mekli, Krisztina A1 - John J McArdle A1 - Margaret Gatz A1 - Armoskus, Chris A1 - James A Knowles A1 - Carol A Prescott KW - Cognitive Ability KW - Genetics KW - GWAS KW - Memory AB - 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. VL - 12 IS - 8 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28800603?dopt=Abstract ER - TY - JOUR T1 - Genome-Wide Association Study of Loneliness Demonstrates a Role for Common Variation. JF - Neuropsychopharmacology Y1 - 2017 A1 - Gao, Jianjun A1 - Lea K. Davis A1 - Amy B. Hart A1 - Sanchez-Roige, Sandra A1 - Han, Lide A1 - John T. Cacioppo A1 - Abraham A Palmer KW - Aged KW - depression KW - Extraversion, Psychological KW - Female KW - Genome-Wide Association Study KW - Humans KW - Loneliness KW - Male KW - Mental Disorders KW - Middle Aged KW - Neuroticism KW - Phenotype AB -

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.

VL - 42 UR - http://www.nature.com/doifinder/10.1038/npp.2016.197 IS - 4 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27629369?dopt=Abstract JO - Neuropsychopharmacology ER - TY - JOUR T1 - Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity. JF - Nature Communications Y1 - 2017 A1 - Joshi, Peter K A1 - Nicola Pirastu A1 - Kentistou, Katherine A A1 - Fischer, Krista A1 - Edith Hofer A1 - Schraut, Katharina E A1 - Clark, David W A1 - Nutile, Teresa A1 - Barnes, Catriona L K A1 - Paul Rhj Timmers A1 - Shen, Xia A1 - Gandin, Ilaria A1 - McDaid, Aaron F A1 - Hansen, Thomas Folkmann A1 - Gordon, Scott D A1 - Giulianini, Franco A1 - Boutin, Thibaud S A1 - Abdellaoui, Abdel A1 - Zhao, Wei A1 - Medina-Gomez, Carolina A1 - Traci M Bartz A1 - Trompet, Stella A1 - Leslie A Lange A1 - Raffield, Laura A1 - van der Spek, Ashley A1 - Galesloot, Tessel E A1 - Proitsi, Petroula A1 - Yanek, Lisa R A1 - Bielak, Lawrence F A1 - Payton, Antony A1 - Murgia, Federico A1 - Concas, Maria Pina A1 - Biino, Ginevra A1 - Tajuddin, Salman M A1 - Seppälä, Ilkka A1 - Amin, Najaf A1 - Boerwinkle, Eric A1 - Børglum, Anders D A1 - Campbell, Archie A1 - Ellen W Demerath A1 - Demuth, Ilja A1 - Jessica Faul A1 - Ford, Ian A1 - Gialluisi, Alessandro A1 - Gögele, Martin A1 - Graff, Mariaelisa A1 - Aroon Hingorani A1 - Jouke-Jan Hottenga A1 - Hougaard, David M A1 - Hurme, Mikko A A1 - Ikram, M Arfan A1 - Jylhä, Marja A1 - Kuh, Diana A1 - Ligthart, Lannie A1 - Lill, Christina M A1 - Lindenberger, Ulman A1 - Lumley, Thomas A1 - Mägi, Reedik A1 - Marques-Vidal, Pedro A1 - Sarah E Medland A1 - Lili Milani A1 - Nagy, Reka A1 - William E R Ollier A1 - Peyser, Patricia A A1 - Pramstaller, Peter P A1 - Ridker, Paul M A1 - Fernando Rivadeneira A1 - Ruggiero, Daniela A1 - Saba, Yasaman A1 - Schmidt, Reinhold A1 - Schmidt, Helena A1 - Slagboom, P Eline A1 - Smith, Blair H A1 - Smith, Jennifer A A1 - Sotoodehnia, Nona A1 - Steinhagen-Thiessen, Elisabeth A1 - van Rooij, Frank J A A1 - Verbeek, André L A1 - Vermeulen, Sita H A1 - Vollenweider, Peter A1 - Wang, Yunpeng A1 - Werge, Thomas A1 - Whitfield, John B A1 - Alan B Zonderman A1 - Lehtimäki, Terho A1 - Michele K Evans A1 - Pirastu, Mario A1 - Fuchsberger, Christian A1 - Bertram, Lars A1 - Pendleton, Neil A1 - Sharon L R Kardia A1 - Ciullo, Marina A1 - Becker, Diane M A1 - Wong, Andrew A1 - Psaty, Bruce M A1 - Cornelia M van Duijn A1 - Wilson, James G A1 - Jukema, J Wouter A1 - Lambertus A Kiemeney A1 - André G Uitterlinden A1 - Franceschini, Nora A1 - Kari E North A1 - David R Weir A1 - Andres Metspalu A1 - Dorret I Boomsma A1 - Caroline Hayward A1 - Daniel I Chasman A1 - Nicholas G Martin A1 - Sattar, Naveed A1 - Campbell, Harry A1 - Tõnu Esko A1 - Kutalik, Zoltán A1 - James F Wilson KW - Alleles KW - Body Mass Index KW - Coronary Disease KW - Education KW - Genetic Predisposition to Disease KW - Genome-Wide Association Study KW - HLA-DQ alpha-Chains KW - HLA-DRB1 Chains KW - Humans KW - Insulin Resistance KW - Life Style KW - Lipoprotein(a) KW - Lipoproteins, HDL KW - Longevity KW - Lung Neoplasms KW - Obesity KW - Polymorphism, Single Nucleotide KW - Smoking KW - Socioeconomic factors AB -

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.

VL - 8 IS - 1 ER - TY - JOUR T1 - Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function. JF - Nat Commun Y1 - 2016 A1 - Pattaro, Cristian A1 - Teumer, Alexander A1 - Gorski, Mathias A1 - Chu, Audrey Y A1 - Li, Man A1 - Mijatovic, Vladan A1 - Garnaas, Maija A1 - Tin, Adrienne A1 - Sorice, Rossella A1 - Yong Li A1 - Taliun, Daniel A1 - Olden, Matthias A1 - Foster, Meredith A1 - Qiong Yang A1 - Chen, Ming-Huei A1 - Pers, Tune H A1 - Andrew D Johnson A1 - Ko, Yi-An A1 - Fuchsberger, Christian A1 - Bamidele O Tayo A1 - Michael A Nalls A1 - Feitosa, Mary F A1 - Isaacs, Aaron A1 - Dehghan, Abbas A1 - d'Adamo, Pio A1 - Adebawole Adeyemo A1 - Dieffenbach, Aida Karina A1 - Alan B Zonderman A1 - Ilja M Nolte A1 - van der Most, Peter J A1 - Alan F Wright A1 - Alan R Shuldiner A1 - Alanna C Morrison A1 - Hofman, Albert A1 - Albert Vernon Smith A1 - Dreisbach, Albert W A1 - Franke, Andre A1 - André G Uitterlinden A1 - Andres Metspalu A1 - Tönjes, Anke A1 - Lupo, Antonio A1 - Robino, Antonietta A1 - Johansson, Åsa A1 - Demirkan, Ayse A1 - Kollerits, Barbara A1 - Freedman, Barry I A1 - Ponte, Belen A1 - Ben A Oostra A1 - Paulweber, Bernhard A1 - Krämer, Bernhard K A1 - Mitchell, Braxton D A1 - Buckley, Brendan M A1 - Peralta, Carmen A A1 - Caroline Hayward A1 - Helmer, Catherine A1 - Charles N Rotimi A1 - Shaffer, Christian M A1 - Müller, Christian A1 - Cinzia Felicita Sala A1 - Cornelia M van Duijn A1 - Saint-Pierre, Aude A1 - Daniel Ackermann A1 - Daniel Shriner A1 - Ruggiero, Daniela A1 - Toniolo, Daniela A1 - Lu, Yingchang A1 - Cusi, Daniele A1 - Czamara, Darina A1 - Ellinghaus, David A1 - David S Siscovick A1 - Ruderfer, Douglas A1 - Gieger, Christian A1 - Grallert, Harald A1 - Rochtchina, Elena A1 - Atkinson, Elizabeth J A1 - Holliday, Elizabeth G A1 - Boerwinkle, Eric A1 - Salvi, Erika A1 - Erwin P Bottinger A1 - Murgia, Federico A1 - Fernando Rivadeneira A1 - Ernst, Florian A1 - Kronenberg, Florian A1 - Hu, Frank B A1 - Navis, Gerjan J A1 - Curhan, Gary C A1 - Georg B Ehret A1 - Homuth, Georg A1 - Coassin, Stefan A1 - Thun, Gian-Andri A1 - Pistis, Giorgio A1 - Gambaro, Giovanni A1 - Malerba, Giovanni A1 - Grant W Montgomery A1 - Guðny Eiríksdóttir A1 - Jacobs, Gunnar A1 - Guo Li A1 - Wichmann, H-Erich A1 - Campbell, Harry A1 - Schmidt, Helena A1 - Wallaschofski, Henri A1 - Völzke, Henry A1 - Brenner, Hermann A1 - Kroemer, Heyo K A1 - Kramer, Holly A1 - Lin, Honghuang A1 - Irene Mateo Leach A1 - Ford, Ian A1 - Guessous, Idris A1 - Rudan, Igor A1 - Prokopenko, Inga A1 - Ingrid B Borecki A1 - Iris M Heid A1 - Kolcic, Ivana A1 - Persico, Ivana A1 - Jukema, J Wouter A1 - James F Wilson A1 - Felix, Janine F A1 - Divers, Jasmin A1 - Lambert, Jean-Charles A1 - Stafford, Jeanette M A1 - Gaspoz, Jean-Michel A1 - Jennifer A Smith A1 - Jessica Faul A1 - Wang, Jie Jin A1 - Ding, Jingzhong A1 - Joel N Hirschhron A1 - John R. Attia A1 - Whitfield, John B A1 - Chalmers, John A1 - Viikari, Jorma A1 - Coresh, Josef A1 - Denny, Joshua C A1 - Karjalainen, Juha A1 - Fernandes, Jyotika K A1 - Endlich, Karlhans A1 - Butterbach, Katja A1 - Keene, Keith L A1 - Kurt Lohman A1 - Portas, Laura A1 - Lenore J Launer A1 - Lyytikäinen, Leo-Pekka A1 - Yengo, Loic A1 - Lude L Franke A1 - Luigi Ferrucci A1 - Rose, Lynda M A1 - Kedenko, Lyudmyla A1 - Rao, Madhumathi A1 - Struchalin, Maksim A1 - Kleber, Marcus E A1 - Cavalieri, Margherita A1 - Haun, Margot A1 - Marilyn C Cornelis A1 - Ciullo, Marina A1 - Pirastu, Mario A1 - de Andrade, Mariza A1 - McEvoy, Mark A A1 - Woodward, Mark A1 - Adam, Martin A1 - Cocca, Massimiliano A1 - Nauck, Matthias A1 - Imboden, Medea A1 - Waldenberger, Melanie A1 - Pruijm, Menno A1 - Metzger, Marie A1 - Stumvoll, Michael A1 - Michele K Evans A1 - Sale, Michele M A1 - Kähönen, Mika A1 - Boban, Mladen A1 - Bochud, Murielle A1 - Rheinberger, Myriam A1 - Verweij, Niek A1 - Bouatia-Naji, Nabila A1 - Nicholas G Martin A1 - Nicholas D Hastie A1 - Nicole M Probst-Hensch A1 - Soranzo, Nicole A1 - Devuyst, Olivier A1 - Olli T Raitakari A1 - Gottesman, Omri A1 - Franco, Oscar H A1 - Polasek, Ozren A1 - Paolo P. Gasparini A1 - Munroe, Patricia B A1 - Ridker, Paul M A1 - Mitchell, Paul A1 - Muntner, Paul A1 - Meisinger, Christa A1 - Johannes H Smit A1 - Kovacs, Peter A1 - Wild, Philipp S A1 - Froguel, Philippe A1 - Rettig, Rainer A1 - Mägi, Reedik A1 - Biffar, Reiner A1 - Schmidt, Reinhold A1 - Middelberg, Rita P S A1 - Carroll, Robert J A1 - Brenda W J H Penninx A1 - Rodney J Scott A1 - Katz, Ronit A1 - Sedaghat, Sanaz A1 - Sarah Wild A1 - Sharon L R Kardia A1 - Ulivi, Sheila A1 - Hwang, Shih-Jen A1 - Enroth, Stefan A1 - Kloiber, Stefan A1 - Trompet, Stella A1 - Stengel, Benedicte A1 - Hancock, Stephen J A1 - Stephen T Turner A1 - Rosas, Sylvia E A1 - Stracke, Sylvia A1 - Tamara B Harris A1 - Zeller, Tanja A1 - Zemunik, Tatijana A1 - Lehtimäki, Terho A1 - Illig, Thomas A1 - Aspelund, Thor A1 - Nikopensius, Tiit A1 - Tõnu Esko A1 - Toshiko Tanaka A1 - Gyllensten, Ulf A1 - Völker, Uwe A1 - Emilsson, Valur A1 - Vitart, Veronique A1 - Aalto, Ville A1 - Gudnason, Vilmundur A1 - Chouraki, Vincent A1 - Chen, Wei-Min A1 - Igl, Wilmar A1 - März, Winfried A1 - Koenig, Wolfgang A1 - Lieb, Wolfgang A1 - Ruth J F Loos A1 - Yongmei Liu A1 - Snieder, Harold A1 - Pramstaller, Peter P A1 - Parsa, Afshin A1 - Jeff O'Connell A1 - Susztak, Katalin A1 - Hamet, Pavel A1 - Tremblay, Johanne A1 - de Boer, Ian H A1 - Böger, Carsten A A1 - Goessling, Wolfram A1 - Daniel I Chasman A1 - Köttgen, Anna A1 - Kao, W H Linda A1 - Caroline S Fox KW - Chronic disease KW - Genome-Wide Association Study KW - Genotype KW - Humans AB -

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.

VL - 7 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26831199?dopt=Abstract ER - TY - JOUR T1 - Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. JF - Nat Genet Y1 - 2016 A1 - Okbay, Aysu A1 - Baselmans, Bart M L A1 - De Neve, Jan-Emmanuel A1 - Turley, Patrick A1 - Nivard, Michel G A1 - Mark Alan Fontana A1 - Meddens, S Fleur W A1 - Richard Karlsson Linnér A1 - Cornelius A Rietveld A1 - Derringer, Jaime A1 - Gratten, Jacob A1 - Lee, James J A1 - Liu, Jimmy Z A1 - de Vlaming, Ronald A1 - Ahluwalia, Tarunveer S A1 - Buchwald, Jadwiga A1 - Cavadino, Alana A1 - Frazier-Wood, Alexis C A1 - Furlotte, Nicholas A A1 - Garfield, Victoria A1 - Geisel, Marie Henrike A1 - Gonzalez, Juan R A1 - Haitjema, Saskia A1 - Karlsson, Robert A1 - van der Laan, Sander W A1 - Ladwig, Karl-Heinz A1 - J. Lahti A1 - Sven J van der Lee A1 - Penelope A Lind A1 - Tian Liu A1 - Lindsay K Matteson A1 - Mihailov, Evelin A1 - Michael B Miller A1 - Minica, Camelia C A1 - Ilja M Nolte A1 - Dennis O Mook-Kanamori A1 - van der Most, Peter J A1 - Christopher J Oldmeadow A1 - Qian, Yong A1 - Olli T Raitakari A1 - Rawal, Rajesh A1 - Realo, Anu A1 - Rueedi, Rico A1 - Schmidt, Börge A1 - Albert Vernon Smith A1 - Stergiakouli, Evie A1 - Toshiko Tanaka A1 - Kent D Taylor A1 - Wedenoja, Juho A1 - Jürgen Wellmann A1 - Westra, Harm-Jan A1 - Willems, Sara M A1 - Wei Zhao A1 - Amin, Najaf A1 - Bakshi, Andrew A1 - Patricia A. Boyle A1 - Cherney, Samantha A1 - Cox, Simon R A1 - Gail Davies A1 - Davis, Oliver S P A1 - Ding, Jun A1 - Nese Direk A1 - Eibich, Peter A1 - Emeny, Rebecca T A1 - Fatemifar, Ghazaleh A1 - Jessica Faul A1 - Luigi Ferrucci A1 - Andreas J Forstner A1 - Gieger, Christian A1 - Gupta, Richa A1 - Tamara B Harris A1 - Harris, Juliette M A1 - Holliday, Elizabeth G A1 - Jouke-Jan Hottenga A1 - Philip L de Jager A1 - Marika A Kaakinen A1 - Kajantie, Eero A1 - Karhunen, Ville A1 - Kolcic, Ivana A1 - Kumari, Meena A1 - Lenore J Launer A1 - Lude L Franke A1 - Li-Gao, Ruifang A1 - Koini, Marisa A1 - Loukola, Anu A1 - Marques-Vidal, Pedro A1 - Grant W Montgomery A1 - Mosing, Miriam A A1 - Paternoster, Lavinia A1 - Pattie, Alison A1 - Katja E Petrovic A1 - Pulkki-Raback, Laura A1 - Quaye, Lydia A1 - Katri Räikkönen A1 - Rudan, Igor A1 - Rodney J Scott A1 - Jennifer A Smith A1 - Angelina R Sutin A1 - Trzaskowski, Maciej A1 - Anna A E Vinkhuyzen A1 - Lei Yu A1 - Zabaneh, Delilah A1 - John R. Attia A1 - David A Bennett A1 - Klaus Berger A1 - Bertram, Lars A1 - Dorret I Boomsma A1 - Snieder, Harold A1 - Chang, Shun-Chiao A1 - Francesco Cucca A1 - Ian J Deary A1 - Cornelia M van Duijn A1 - Johan G Eriksson A1 - Bültmann, Ute A1 - Eco J. C. de Geus A1 - Groenen, Patrick J F A1 - Gudnason, Vilmundur A1 - Hansen, Torben A1 - Catharina A Hartman A1 - Haworth, Claire M A A1 - Caroline Hayward A1 - Andrew C Heath A1 - Hinds, David A A1 - Hyppönen, Elina A1 - Iacono, William G A1 - Järvelin, Marjo-Riitta A1 - Jöckel, Karl-Heinz A1 - Kaprio, Jaakko A1 - Sharon L R Kardia A1 - Keltikangas-Järvinen, Liisa A1 - Kraft, Peter A1 - Laura D Kubzansky A1 - Lehtimäki, Terho A1 - Patrik K E Magnusson A1 - Nicholas G Martin A1 - McGue, Matt A1 - Andres Metspalu A1 - Melinda C Mills A1 - de Mutsert, Renée A1 - Oldehinkel, Albertine J A1 - Pasterkamp, Gerard A1 - Nancy L Pedersen A1 - Plomin, Robert A1 - Polasek, Ozren A1 - Power, Christine A1 - Rich, Stephen S A1 - Rosendaal, Frits R A1 - Hester M. den Ruijter A1 - Schlessinger, David A1 - Schmidt, Helena A1 - Svento, Rauli A1 - Schmidt, Reinhold A1 - Alizadeh, Behrooz Z A1 - Thorkild I. A. Sørensen A1 - Timothy Spector A1 - Andrew Steptoe A1 - Antonio Terracciano A1 - A. Roy Thurik A1 - Nicholas J Timpson A1 - Henning Tiemeier A1 - André G Uitterlinden A1 - Vollenweider, Peter A1 - Wagner, Gert G A1 - David R Weir A1 - Yang, Jian A1 - Dalton C Conley A1 - Hofman, Albert A1 - Johannesson, Magnus A1 - David I Laibson A1 - Sarah E Medland A1 - Meyer, Michelle N A1 - Pickrell, Joseph K A1 - Tõnu Esko A1 - Krueger, Robert F A1 - Jonathan P. Beauchamp A1 - Philipp D Koellinger A1 - Daniel J. Benjamin A1 - Bartels, Meike A1 - Cesarini, David KW - Anxiety Disorders KW - Bayes Theorem KW - depression KW - Genome-Wide Association Study KW - Humans KW - Neuroticism KW - Phenotype KW - Polymorphism, Single Nucleotide AB -

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.

VL - 48 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27089181?dopt=Abstract ER - TY - JOUR T1 - Genome-wide analysis identifies 12 loci influencing human reproductive behavior. JF - Nat Genet Y1 - 2016 A1 - Nicola Barban A1 - Jansen, Rick A1 - de Vlaming, Ronald A1 - Vaez, Ahmad A1 - Mandemakers, Jornt J A1 - Felix C Tropf A1 - Shen, Xia A1 - James F Wilson A1 - Daniel I Chasman A1 - Ilja M Nolte A1 - Tragante, Vinicius A1 - van der Laan, Sander W A1 - Perry, John R B A1 - Kong, Augustine A1 - Ahluwalia, Tarunveer S A1 - Albrecht, Eva A1 - Laura M Yerges-Armstrong A1 - Atzmon, Gil A1 - Auro, Kirsi A1 - Kristin L. Ayers A1 - Bakshi, Andrew A1 - Ben-Avraham, Danny A1 - Klaus Berger A1 - Bergman, Aviv A1 - Bertram, Lars A1 - Bielak, Lawrence F A1 - Bjornsdottir, Gyda A1 - Bonder, Marc Jan A1 - Broer, Linda A1 - Bui, Minh A1 - Barbieri, Caterina A1 - Cavadino, Alana A1 - Chavarro, Jorge E A1 - Turman, Constance A1 - Maria Pina Concas A1 - Cordell, Heather J A1 - Gail Davies A1 - Eibich, Peter A1 - Eriksson, Nicholas A1 - Tõnu Esko A1 - Eriksson, Joel A1 - Falahi, Fahimeh A1 - Felix, Janine F A1 - Mark Alan Fontana A1 - Lude L Franke A1 - Gandin, Ilaria A1 - Gaskins, Audrey J A1 - Gieger, Christian A1 - Gunderson, Erica P A1 - Guo, Xiuqing A1 - Caroline Hayward A1 - He, Chunyan A1 - Edith Hofer A1 - Huang, Hongyan A1 - Joshi, Peter K A1 - Kanoni, Stavroula A1 - Karlsson, Robert A1 - Kiechl, Stefan A1 - Kifley, Annette A1 - Kluttig, Alexander A1 - Kraft, Peter A1 - Lagou, Vasiliki A1 - Lecoeur, Cecile A1 - Lahti, Jari A1 - Li-Gao, Ruifang A1 - Penelope A Lind A1 - Tian Liu A1 - Makalic, Enes A1 - Mamasoula, Crysovalanto A1 - Lindsay K Matteson A1 - Mbarek, Hamdi A1 - McArdle, Patrick F A1 - McMahon, George A1 - Meddens, S Fleur W A1 - Mihailov, Evelin A1 - Michael B Miller A1 - Missmer, Stacey A A1 - Monnereau, Claire A1 - van der Most, Peter J A1 - Myhre, Ronny A1 - Michael A Nalls A1 - Nutile, Teresa A1 - Ioanna Panagiota Kalafati A1 - Porcu, Eleonora A1 - Prokopenko, Inga A1 - Rajan, Kumar B A1 - Rich-Edwards, Janet A1 - Cornelius A Rietveld A1 - Robino, Antonietta A1 - Rose, Lynda M A1 - Rueedi, Rico A1 - Ryan, Kathleen A A1 - Saba, Yasaman A1 - Schmidt, Daniel A1 - Jennifer A Smith A1 - Stolk, Lisette A1 - Streeten, Elizabeth A1 - Tönjes, Anke A1 - Thorleifsson, Gudmar A1 - Ulivi, Sheila A1 - Wedenoja, Juho A1 - Jürgen Wellmann A1 - Willeit, Peter A1 - Yao, Jie A1 - Yengo, Loic A1 - Jing Hua Zhao A1 - Wei Zhao A1 - Zhernakova, Daria V A1 - Amin, Najaf A1 - Andrews, Howard A1 - Balkau, Beverley A1 - Barzilai, Nir A1 - Bergmann, Sven A1 - Biino, Ginevra A1 - Bisgaard, Hans A1 - Bønnelykke, Klaus A1 - Dorret I Boomsma A1 - Buring, Julie E A1 - Campbell, Harry A1 - Cappellani, Stefania A1 - Ciullo, Marina A1 - Cox, Simon R A1 - Francesco Cucca A1 - Toniolo, Daniela A1 - Davey-Smith, George A1 - Ian J Deary A1 - George Dedoussis A1 - Deloukas, Panos A1 - Cornelia M van Duijn A1 - Eco J. C. de Geus A1 - Johan G Eriksson A1 - Jessica Faul A1 - Cinzia Felicita Sala A1 - Froguel, Philippe A1 - Paolo P. Gasparini A1 - Giorgia G Girotto A1 - Hans-Jörgen Grabe A1 - Greiser, Karin Halina A1 - Groenen, Patrick J F A1 - de Haan, Hugoline G A1 - Haerting, Johannes A1 - Tamara B Harris A1 - Andrew C Heath A1 - Heikkilä, Kauko A1 - Hofman, Albert A1 - Homuth, Georg A1 - Holliday, Elizabeth G A1 - John L Hopper A1 - Hyppönen, Elina A1 - Jacobsson, Bo A1 - Vincent Jaddoe A1 - Johannesson, Magnus A1 - Jugessur, Astanand A1 - Kähönen, Mika A1 - Kajantie, Eero A1 - Sharon L R Kardia A1 - Keavney, Bernard A1 - Kolcic, Ivana A1 - Koponen, Päivikki A1 - Kovacs, Peter A1 - Kronenberg, Florian A1 - Kutalik, Zoltán A1 - La Bianca, Martina A1 - Lachance, Genevieve A1 - Iacono, William G A1 - Lai, Sandra A1 - Lehtimäki, Terho A1 - David C Liewald A1 - Lindgren, Cecilia M A1 - Yongmei Liu A1 - Luben, Robert A1 - Lucht, Michael A1 - Luoto, Riitta A1 - Magnus, Per A1 - Patrik K E Magnusson A1 - Nicholas G Martin A1 - McGue, Matt A1 - McQuillan, Ruth A1 - Sarah E Medland A1 - Meisinger, Christa A1 - Mellström, Dan A1 - Andres Metspalu A1 - Traglia, Michela A1 - Lili Milani A1 - Mitchell, Paul A1 - Grant W Montgomery A1 - Dennis O Mook-Kanamori A1 - de Mutsert, Renée A1 - Nohr, Ellen A A1 - Ohlsson, Claes A1 - Olsen, Jørn A1 - Ong, Ken K A1 - Paternoster, Lavinia A1 - Pattie, Alison A1 - Brenda W J H Penninx A1 - Markus Perola A1 - Peyser, Patricia A A1 - Pirastu, Mario A1 - Polasek, Ozren A1 - Power, Chris A1 - Kaprio, Jaakko A1 - Raffel, Leslie J A1 - Katri Räikkönen A1 - Olli T Raitakari A1 - Ridker, Paul M A1 - Ring, Susan M A1 - Roll, Kathryn A1 - Rudan, Igor A1 - Ruggiero, Daniela A1 - Rujescu, Dan A1 - Veikko Salomaa A1 - Schlessinger, David A1 - Schmidt, Helena A1 - Schmidt, Reinhold A1 - Schupf, Nicole A1 - Johannes H Smit A1 - Sorice, Rossella A1 - Timothy Spector A1 - John M Starr A1 - Stöckl, Doris A1 - Strauch, Konstantin A1 - Stumvoll, Michael A1 - Swertz, Morris A A1 - Thorsteinsdottir, Unnur A1 - A. Roy Thurik A1 - Nicholas J Timpson A1 - Tung, Joyce Y A1 - André G Uitterlinden A1 - Vaccargiu, Simona A1 - Viikari, Jorma A1 - Vitart, Veronique A1 - Völzke, Henry A1 - Vollenweider, Peter A1 - Vuckovic, Dragana A1 - Waage, Johannes A1 - Wagner, Gert G A1 - Wang, Jie Jin A1 - Wareham, Nicholas J A1 - David R Weir A1 - Gonneke Willemsen A1 - Willeit, Johann A1 - Alan F Wright A1 - Krina T Zondervan A1 - Stefansson, Kari A1 - Krueger, Robert F A1 - Lee, James J A1 - Daniel J. Benjamin A1 - Cesarini, David A1 - Philipp D Koellinger A1 - den Hoed, Marcel A1 - Snieder, Harold A1 - Melinda C Mills AB -

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.

VL - 48 IS - 12 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27798627?dopt=Abstract ER - TY - JOUR T1 - GENOME-WIDE ASSOCIATION STUDY (GWAS) AND GENOME-WIDE BY ENVIRONMENT INTERACTION STUDY (GWEIS) OF DEPRESSIVE SYMPTOMS IN AFRICAN AMERICAN AND HISPANIC/LATINA WOMEN. JF - Depress Anxiety Y1 - 2016 A1 - Dunn, Erin C A1 - Wiste, Anna A1 - Radmanesh, Farid A1 - Almli, Lynn M A1 - Gogarten, Stephanie M A1 - Sofer, Tamar A1 - Jessica Faul A1 - Sharon L R Kardia A1 - Jennifer A Smith A1 - David R Weir A1 - Wei Zhao A1 - Soare, Thomas W A1 - Saira S Mirza A1 - Karin Hek A1 - Henning Tiemeier A1 - Goveas, Joseph S A1 - Sarto, Gloria E A1 - Snively, Beverly M A1 - Marilyn C Cornelis A1 - Karestan C Koenen A1 - Kraft, Peter A1 - Shaun M Purcell A1 - Ressler, Kerry J A1 - Rosand, Jonathan A1 - Wassertheil-Smoller, Sylvia A1 - Smoller, Jordan W KW - African Americans KW - Aged KW - depression KW - Female KW - Gene-Environment Interaction KW - Genome-Wide Association Study KW - Hispanic Americans KW - Humans KW - Life Change Events KW - Middle Aged KW - Phenotype KW - Polymorphism, Single Nucleotide KW - Risk Factors KW - Self Report AB -

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.

VL - 33 IS - 4 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27038408?dopt=Abstract ER - TY - JOUR T1 - Genome-wide association study identifies 74 loci associated with educational attainment. JF - Nature Y1 - 2016 A1 - Okbay, Aysu A1 - Jonathan P. Beauchamp A1 - Mark Alan Fontana A1 - Lee, James J A1 - Pers, Tune H A1 - Cornelius A Rietveld A1 - Turley, Patrick A1 - Chen, Guo-Bo A1 - Emilsson, Valur A1 - Meddens, S Fleur W A1 - Oskarsson, Sven A1 - Pickrell, Joseph K A1 - Thom, Kevin A1 - Pascal N Timshel A1 - de Vlaming, Ronald A1 - Abdel Abdellaoui A1 - Ahluwalia, Tarunveer S A1 - Bacelis, Jonas A1 - Baumbach, Clemens A1 - Bjornsdottir, Gyda A1 - Brandsma, Johannes H A1 - Maria Pina Concas A1 - Derringer, Jaime A1 - Furlotte, Nicholas A A1 - Galesloot, Tessel E A1 - Giorgia G Girotto A1 - Gupta, Richa A1 - Hall, Leanne M A1 - Sarah E Harris A1 - Edith Hofer A1 - Horikoshi, Momoko A1 - Huffman, Jennifer E A1 - Kaasik, Kadri A1 - Ioanna Panagiota Kalafati A1 - Karlsson, Robert A1 - Kong, Augustine A1 - Lahti, Jari A1 - Sven J van der Lee A1 - Christiaan de Leeuw A1 - Penelope A Lind A1 - Lindgren, Karl-Oskar A1 - Tian Liu A1 - Mangino, Massimo A1 - Marten, Jonathan A1 - Mihailov, Evelin A1 - Michael B Miller A1 - van der Most, Peter J A1 - Christopher J Oldmeadow A1 - Payton, Antony A1 - Pervjakova, Natalia A1 - Wouter J Peyrot A1 - Qian, Yong A1 - Olli T Raitakari A1 - Rueedi, Rico A1 - Salvi, Erika A1 - Schmidt, Börge A1 - Schraut, Katharina E A1 - Jianxin Shi A1 - Albert Vernon Smith A1 - Poot, Raymond A A1 - St Pourcain, Beate A1 - Teumer, Alexander A1 - Thorleifsson, Gudmar A1 - Verweij, Niek A1 - Vuckovic, Dragana A1 - Jürgen Wellmann A1 - Westra, Harm-Jan A1 - Yang, Jingyun A1 - Wei Zhao A1 - Zhihong Zhu A1 - Alizadeh, Behrooz Z A1 - Amin, Najaf A1 - Bakshi, Andrew A1 - Baumeister, Sebastian E A1 - Biino, Ginevra A1 - Bønnelykke, Klaus A1 - Patricia A. Boyle A1 - Campbell, Harry A1 - Cappuccio, Francesco P A1 - Gail Davies A1 - De Neve, Jan-Emmanuel A1 - Deloukas, Panos A1 - Demuth, Ilja A1 - Ding, Jun A1 - Eibich, Peter A1 - Eisele, Lewin A1 - Eklund, Niina A1 - Jessica Faul A1 - Feitosa, Mary F A1 - Andreas J Forstner A1 - Gandin, Ilaria A1 - Gunnarsson, Bjarni A1 - Halldórsson, Bjarni V A1 - Tamara B Harris A1 - Andrew C Heath A1 - Lynne J Hocking A1 - Holliday, Elizabeth G A1 - Homuth, Georg A1 - Horan, Michael A A1 - Jouke-Jan Hottenga A1 - Philip L de Jager A1 - Joshi, Peter K A1 - Jugessur, Astanand A1 - Marika A Kaakinen A1 - Kähönen, Mika A1 - Kanoni, Stavroula A1 - Keltigangas-Järvinen, Liisa A1 - Lambertus A Kiemeney A1 - Kolcic, Ivana A1 - Koskinen, Seppo A1 - Kraja, Aldi T A1 - Kroh, Martin A1 - Kutalik, Zoltán A1 - Latvala, Antti A1 - Lenore J Launer A1 - Lebreton, Maël P A1 - Douglas F Levinson A1 - Paul Lichtenstein A1 - Lichtner, Peter A1 - David C Liewald A1 - Loukola, Anu A1 - Pamela A F Madden A1 - Mägi, Reedik A1 - Mäki-Opas, Tomi A1 - Riccardo E Marioni A1 - Marques-Vidal, Pedro A1 - Meddens, Gerardus A A1 - McMahon, George A1 - Meisinger, Christa A1 - Meitinger, Thomas A1 - Milaneschi, Yusplitri A1 - Lili Milani A1 - Grant W Montgomery A1 - Myhre, Ronny A1 - Nelson, Christopher P A1 - Nyholt, Dale R A1 - William E R Ollier A1 - Aarno Palotie A1 - Paternoster, Lavinia A1 - Nancy L Pedersen A1 - Katja E Petrovic A1 - David J Porteous A1 - Katri Räikkönen A1 - Ring, Susan M A1 - Robino, Antonietta A1 - Rostapshova, Olga A1 - Rudan, Igor A1 - Rustichini, Aldo A1 - Veikko Salomaa A1 - Sanders, Alan R A1 - Sarin, Antti-Pekka A1 - Schmidt, Helena A1 - Rodney J Scott A1 - Smith, Blair H A1 - Jennifer A Smith A1 - Staessen, Jan A A1 - Steinhagen-Thiessen, Elisabeth A1 - Strauch, Konstantin A1 - Antonio Terracciano A1 - Tobin, Martin D A1 - Ulivi, Sheila A1 - Vaccargiu, Simona A1 - Quaye, Lydia A1 - van Rooij, Frank J A A1 - Venturini, Cristina A1 - Anna A E Vinkhuyzen A1 - Völker, Uwe A1 - Völzke, Henry A1 - Vonk, Judith M A1 - Vozzi, Diego A1 - Waage, Johannes A1 - Erin B Ware A1 - Gonneke Willemsen A1 - John R. Attia A1 - David A Bennett A1 - Klaus Berger A1 - Bertram, Lars A1 - Bisgaard, Hans A1 - Dorret I Boomsma A1 - Ingrid B Borecki A1 - Bültmann, Ute A1 - Chabris, Christopher F A1 - Francesco Cucca A1 - Cusi, Daniele A1 - Ian J Deary A1 - George Dedoussis A1 - Cornelia M van Duijn A1 - Johan G Eriksson A1 - Franke, Barbara A1 - Lude L Franke A1 - Paolo P. Gasparini A1 - Gejman, Pablo V A1 - Gieger, Christian A1 - Hans-Jörgen Grabe A1 - Gratten, Jacob A1 - Groenen, Patrick J F A1 - Gudnason, Vilmundur A1 - van der Harst, Pim A1 - Caroline Hayward A1 - Hinds, David A A1 - Hoffmann, Wolfgang A1 - Hyppönen, Elina A1 - Iacono, William G A1 - Jacobsson, Bo A1 - Järvelin, Marjo-Riitta A1 - Jöckel, Karl-Heinz A1 - Kaprio, Jaakko A1 - Sharon L R Kardia A1 - Lehtimäki, Terho A1 - Lehrer, Steven F A1 - Patrik K E Magnusson A1 - Nicholas G Martin A1 - McGue, Matt A1 - Andres Metspalu A1 - Pendleton, Neil A1 - Brenda W J H Penninx A1 - Markus Perola A1 - Nicola Pirastu A1 - Pirastu, Mario A1 - Polasek, Ozren A1 - Posthuma, Danielle A1 - Power, Christine A1 - Province, Michael A A1 - Nilesh J Samani A1 - Schlessinger, David A1 - Schmidt, Reinhold A1 - Thorkild I. A. Sørensen A1 - Timothy Spector A1 - Stefansson, Kari A1 - Thorsteinsdottir, Unnur A1 - A. Roy Thurik A1 - Nicholas J Timpson A1 - Henning Tiemeier A1 - Tung, Joyce Y A1 - André G Uitterlinden A1 - Vitart, Veronique A1 - Vollenweider, Peter A1 - David R Weir A1 - James F Wilson A1 - Alan F Wright A1 - Dalton C Conley A1 - Krueger, Robert F A1 - George Davey Smith A1 - Hofman, Albert A1 - David I Laibson A1 - Sarah E Medland A1 - Meyer, Michelle N A1 - Yang, Jian A1 - Johannesson, Magnus A1 - Peter M Visscher A1 - Tõnu Esko A1 - Philipp D Koellinger A1 - Cesarini, David A1 - Daniel J. Benjamin KW - Alzheimer's disease KW - Bipolar Disorder KW - Cognitive Ability KW - Education KW - Fetus KW - Genome-Wide Association Study KW - Humans KW - Molecular Sequence Annotation KW - Polymorphism, Single Nucleotide KW - Schizophrenia KW - United Kingdom AB -

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.

VL - 533 IS - 7604 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27225129?dopt=Abstract ER - TY - JOUR T1 - GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium. JF - Aging Cell Y1 - 2016 A1 - Amy M Matteini A1 - Toshiko Tanaka A1 - Karasik, David A1 - Atzmon, Gil A1 - Chou, Wen-Chi A1 - John D Eicher A1 - Andrew D Johnson A1 - Alice M. Arnold A1 - Michele L Callisaya A1 - Gail Davies A1 - Daniel S Evans A1 - Holtfreter, Birte A1 - Kurt Lohman A1 - Kathryn L Lunetta A1 - Mangino, Massimo A1 - Albert Vernon Smith A1 - Jennifer A Smith A1 - Teumer, Alexander A1 - Lei Yu A1 - Dan E Arking A1 - Aron S Buchman A1 - Chibinik, Lori B A1 - Philip L de Jager A1 - Jessica Faul A1 - Melissa E Garcia A1 - Gillham-Nasenya, Irina A1 - Gudnason, Vilmundur A1 - Hofman, Albert A1 - Hsu, Yi-Hsiang A1 - Ittermann, Till A1 - Lahousse, Lies A1 - David C Liewald A1 - Yongmei Liu A1 - Lopez, Lorna A1 - Fernando Rivadeneira A1 - Rotter, Jerome I A1 - Siggeirsdottir, Kristin A1 - John M Starr A1 - Thomson, Russell A1 - Tranah, Gregory J A1 - André G Uitterlinden A1 - Völker, Uwe A1 - Völzke, Henry A1 - David R Weir A1 - Kristine Yaffe A1 - Wei Zhao A1 - Wei Vivian Zhuang A1 - Zmuda, Joseph M A1 - David A Bennett A1 - Steven R Cummings A1 - Ian J Deary A1 - Luigi Ferrucci A1 - Tamara B Harris A1 - Sharon L R Kardia A1 - Kocher, Thomas A1 - Stephen B Kritchevsky A1 - Psaty, Bruce M A1 - Seshadri, Sudha A1 - Timothy Spector A1 - Velandai K Srikanth A1 - Beverly G Windham A1 - Zillikens, M Carola A1 - Anne B Newman A1 - Jeremy D Walston A1 - Douglas P Kiel A1 - Joanne M Murabito KW - Adult KW - Aged KW - Chromatin Immunoprecipitation KW - Cohort Studies KW - Epigenesis, Genetic KW - Genome-Wide Association Study KW - Hand Strength KW - Humans KW - Molecular Sequence Annotation KW - Muscle Strength KW - Polymorphism, Single Nucleotide KW - Quantitative Trait Loci KW - Reproducibility of Results AB -

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.

VL - 15 IS - 5 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27325353?dopt=Abstract ER - TY - JOUR T1 - Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53949). JF - Mol Psychiatry Y1 - 2015 A1 - Gail Davies A1 - Armstrong, N. A1 - Joshua C. Bis A1 - Bressler, J. A1 - Chouraki, V. A1 - Giddaluru, S. A1 - Edith Hofer A1 - Carla A Ibrahim-Verbaas A1 - Kirin, M. A1 - J. Lahti A1 - Sven J van der Lee A1 - Stephanie Le Hellard A1 - Tian Liu A1 - Riccardo E Marioni A1 - Christopher J Oldmeadow A1 - Postmus, I. A1 - Albert Vernon Smith KW - Aged KW - Aged, 80 and over KW - Atherosclerosis KW - Cognition KW - Cognition Disorders KW - Cohort Studies KW - Female KW - Genetic Predisposition to Disease KW - Genome-Wide Association Study KW - HMGN1 Protein KW - Humans KW - Male KW - Middle Aged KW - Neuropsychological tests KW - Phenotype KW - Polymorphism, Single Nucleotide KW - Scotland AB -

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.

PB - 20 VL - 20 IS - 2 N1 - Times Cited: 0 0 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25644384?dopt=Abstract U2 - PMC4356746 U4 - genetics/genetics/GENOME-WIDE ASSOCIATION/TOMM40/ABCG1/MEF2C/complex train anaysis/Atherosclerosis Risk in Communities Study/cross-national study ER - TY - JOUR T1 - Genetic studies of body mass index yield new insights for obesity biology. JF - Nature Y1 - 2015 A1 - Locke, Adam E A1 - Kahali, Bratati A1 - Berndt, Sonja I A1 - Justice, Anne E A1 - Pers, Tune H A1 - Day, Felix R A1 - Powell, Corey A1 - Vedantam, Sailaja A1 - Buchkovich, Martin L A1 - Yang, Jian A1 - Croteau-Chonka, Damien C A1 - Tõnu Esko A1 - Fall, Tove A1 - Ferreira, Teresa A1 - Gustafsson, Stefan A1 - Kutalik, Zoltán A1 - Luan, Jian'an A1 - Mägi, Reedik A1 - Randall, Joshua C A1 - Thomas W Winkler A1 - Andrew R Wood A1 - Workalemahu, Tsegaselassie A1 - Jessica Faul A1 - Jennifer A Smith A1 - Jing Hua Zhao A1 - Wei Zhao A1 - Chen, Jin A1 - Rudolf Ferhmann A1 - Hedman, Åsa K A1 - Karjalainen, Juha A1 - Schmidt, Ellen M A1 - Absher, Devin A1 - Amin, Najaf A1 - Anderson, Denise A1 - Beekman, Marian A1 - Bolton, Jennifer L A1 - Bragg-Gresham, Jennifer L A1 - Buyske, Steven A1 - Demirkan, Ayse A1 - Deng, Guohong A1 - Georg B Ehret A1 - Feenstra, Bjarke A1 - Feitosa, Mary F A1 - Fischer, Krista A1 - Goel, Anuj A1 - Gong, Jian A1 - Jackson, Anne U A1 - Kanoni, Stavroula A1 - Kleber, Marcus E A1 - Kristiansson, Kati A1 - Lim, Unhee A1 - Lotay, Vaneet A1 - Mangino, Massimo A1 - Irene Mateo Leach A1 - Medina-Gomez, Carolina A1 - Sarah E Medland A1 - Michael A Nalls A1 - Palmer, Cameron D A1 - Pasko, Dorota A1 - Pechlivanis, Sonali A1 - Peters, Marjolein J A1 - Prokopenko, Inga A1 - Shungin, Dmitry A1 - Stančáková, Alena A1 - Strawbridge, Rona J A1 - Yun Ju Sung A1 - Toshiko Tanaka A1 - Teumer, Alexander A1 - Trompet, Stella A1 - van der Laan, Sander W A1 - van Setten, Jessica A1 - Jana V. van Vliet-Ostaptchouk A1 - Wang, Zhaoming A1 - Yengo, Loic A1 - Zhang, Weihua A1 - Isaacs, Aaron A1 - Albrecht, Eva A1 - Ärnlöv, Johan A1 - Arscott, Gillian M A1 - Attwood, Antony P A1 - Bandinelli, Stefania A1 - Barrett, Amy A1 - Bas, Isabelita N A1 - Bellis, Claire A1 - Bennett, Amanda J A1 - Berne, Christian A1 - Blagieva, Roza A1 - Blüher, Matthias A1 - Böhringer, Stefan A1 - Bonnycastle, Lori L A1 - Böttcher, Yvonne A1 - Boyd, Heather A A1 - Bruinenberg, Marcel A1 - Caspersen, Ida H A1 - Yii-Der I Chen A1 - Robert Clark A1 - Daw, E Warwick A1 - de Craen, Anton J M A1 - Delgado, Graciela A1 - Dimitriou, Maria A1 - Doney, Alex S F A1 - Eklund, Niina A1 - Estrada, Karol A1 - Eury, Elodie A1 - Folkersen, Lasse A1 - Fraser, Ross M A1 - Melissa E Garcia A1 - Geller, Frank A1 - Giedraitis, Vilmantas A1 - Gigante, Bruna A1 - Alan S Go A1 - Golay, Alain A1 - Goodall, Alison H A1 - Gordon, Scott D A1 - Gorski, Mathias A1 - Hans-Jörgen Grabe A1 - Grallert, Harald A1 - Grammer, Tanja B A1 - Gräßler, Jürgen A1 - Grönberg, Henrik A1 - Groves, Christopher J A1 - Gusto, Gaëlle A1 - Jeffrey Haessler A1 - Hall, Per A1 - Haller, Toomas A1 - Hallmans, Göran A1 - Catharina A Hartman A1 - Hassinen, Maija A1 - Caroline Hayward A1 - Heard-Costa, Nancy L A1 - Helmer, Quinta A1 - Hengstenberg, Christian A1 - Oddgeir L Holmen A1 - Jouke-Jan Hottenga A1 - James, Alan L A1 - Janina Jeff A1 - Johansson, Åsa A1 - Jolley, Jennifer A1 - Juliusdottir, Thorhildur A1 - Kinnunen, Leena A1 - Koenig, Wolfgang A1 - Koskenvuo, Markku A1 - Kratzer, Wolfgang A1 - Laitinen, Jaana A1 - Lamina, Claudia A1 - Leander, Karin A1 - Lee, Nanette R A1 - Lichtner, Peter A1 - Lars Lind A1 - Lindström, Jaana A1 - Ken Sin Lo A1 - Lobbens, Stéphane A1 - Lorbeer, Roberto A1 - Lu, Yingchang A1 - Mach, François A1 - Patrik K E Magnusson A1 - Mahajan, Anubha A1 - McArdle, Wendy L A1 - McLachlan, Stela A1 - Menni, Cristina A1 - Merger, Sigrun A1 - Mihailov, Evelin A1 - Lili Milani A1 - Moayyeri, Alireza A1 - Monda, Keri L A1 - Morken, Mario A A1 - Mulas, Antonella A1 - Müller, Gabriele A1 - Müller-Nurasyid, Martina A1 - Musk, Arthur W A1 - Nagaraja, Ramaiah A1 - Markus M Nöthen A1 - Ilja M Nolte A1 - Pilz, Stefan A1 - Nigel W Rayner A1 - Renstrom, Frida A1 - Rettig, Rainer A1 - Ried, Janina S A1 - Ripke, Stephan A1 - Neil R Robertson A1 - Rose, Lynda M A1 - Sanna, Serena A1 - Scharnagl, Hubert A1 - Scholtens, Salome A1 - Schumacher, Fredrick R A1 - Scott, William R A1 - Seufferlein, Thomas A1 - Jianxin Shi A1 - Albert Vernon Smith A1 - Smolonska, Joanna A1 - Stanton, Alice V A1 - Steinthorsdottir, Valgerdur A1 - Kathleen E Stirrups A1 - Heather M Stringham A1 - Sundström, Johan A1 - Swertz, Morris A A1 - Swift, Amy J A1 - Syvänen, Ann-Christine A1 - Tan, Sian-Tsung A1 - Bamidele O Tayo A1 - Thorand, Barbara A1 - Thorleifsson, Gudmar A1 - Tyrer, Jonathan P A1 - Uh, Hae-Won A1 - Vandenput, Liesbeth A1 - Verhulst, Frank C A1 - Vermeulen, Sita H A1 - Verweij, Niek A1 - Vonk, Judith M A1 - Lindsay L Waite A1 - Warren, Helen R A1 - Dawn M Waterworth A1 - Michael N Weedon A1 - Wilkens, Lynne R A1 - Willenborg, Christina A1 - Wilsgaard, Tom A1 - Wojczynski, Mary K A1 - Wong, Andrew A1 - Alan F Wright A1 - Zhang, Qunyuan A1 - Brennan, Eoin P A1 - Murim Choi A1 - Dastani, Zari A1 - Alexander W Drong A1 - Eriksson, Per A1 - Franco-Cereceda, Anders A1 - Gådin, Jesper R A1 - Gharavi, Ali G A1 - Goddard, Michael E A1 - Handsaker, Robert E A1 - Huang, Jinyan A1 - Karpe, Fredrik A1 - Kathiresan, Sekar A1 - Keildson, Sarah A1 - Kiryluk, Krzysztof A1 - Kubo, Michiaki A1 - Lee, Jong-Young A1 - Liang, Liming A1 - Lifton, Richard P A1 - Ma, Baoshan A1 - McCarroll, Steven A A1 - McKnight, Amy J A1 - Min, Josine L A1 - Moffatt, Miriam F A1 - Grant W Montgomery A1 - Joanne M Murabito A1 - Nicholson, George A1 - Nyholt, Dale R A1 - Okada, Yukinori A1 - Perry, John R B A1 - Dorajoo, Rajkumar A1 - Reinmaa, Eva A1 - Salem, Rany M A1 - Sandholm, Niina A1 - Scott, Robert A A1 - Stolk, Lisette A1 - Takahashi, Atsushi A1 - Tanaka, Toshihiro A1 - Ferdinand M van 't Hooft A1 - Anna A E Vinkhuyzen A1 - Westra, Harm-Jan A1 - Wei Zhang A1 - Krina T Zondervan A1 - Andrew C Heath A1 - Arveiler, Dominique A1 - Bakker, Stephan J L A1 - Beilby, John A1 - Bergman, Richard N A1 - Blangero, John A1 - Bovet, Pascal A1 - Campbell, Harry A1 - Caulfield, Mark J A1 - Cesana, Giancarlo A1 - Chakravarti, Aravinda A1 - Daniel I Chasman A1 - Chines, Peter S A1 - Collins, Francis S A1 - Crawford, Dana C A1 - Cupples, L Adrienne A1 - Cusi, Daniele A1 - Danesh, John A1 - de Faire, Ulf A1 - Hester M den Ruijter A1 - Dominiczak, Anna F A1 - Erbel, Raimund A1 - Erdmann, Jeanette A1 - Johan G Eriksson A1 - Farrall, Martin A1 - Felix, Stephan B A1 - Ferrannini, Ele A1 - Ferrières, Jean A1 - Ford, Ian A1 - Forouhi, Nita G A1 - Forrester, Terrence A1 - Franco, Oscar H A1 - Gansevoort, Ron T A1 - Gejman, Pablo V A1 - Gieger, Christian A1 - Gottesman, Omri A1 - Gudnason, Vilmundur A1 - Gyllensten, Ulf A1 - Hall, Alistair S A1 - Tamara B Harris A1 - Andrew T Hattersley A1 - Hicks, Andrew A A1 - Hindorff, Lucia A A1 - Aroon Hingorani A1 - Hofman, Albert A1 - Homuth, Georg A1 - Hovingh, G Kees A1 - Humphries, Steve E A1 - Hunt, Steven C A1 - Hyppönen, Elina A1 - Illig, Thomas A1 - Jacobs, Kevin B A1 - Järvelin, Marjo-Riitta A1 - Jöckel, Karl-Heinz A1 - Johansen, Berit A1 - Jousilahti, Pekka A1 - Jukema, J Wouter A1 - Jula, Antti M A1 - Kaprio, Jaakko A1 - Kastelein, John J P A1 - Keinanen-Kiukaanniemi, Sirkka M A1 - Lambertus A Kiemeney A1 - Knekt, Paul A1 - Kooner, Jaspal S A1 - Charles Kooperberg A1 - Kovacs, Peter A1 - Kraja, Aldi T A1 - Kumari, Meena A1 - Kuusisto, Johanna A1 - Lakka, Timo A A1 - Langenberg, Claudia A1 - Loic Le Marchand A1 - Lehtimäki, Terho A1 - Lyssenko, Valeriya A1 - Männistö, Satu A1 - Marette, André A1 - Matise, Tara C A1 - McKenzie, Colin A A1 - McKnight, Barbara A1 - Moll, Frans L A1 - Morris, Andrew D A1 - Morris, Andrew P A1 - Murray, Jeffrey C A1 - Nelis, Mari A1 - Ohlsson, Claes A1 - Oldehinkel, Albertine J A1 - Ong, Ken K A1 - Pamela A F Madden A1 - Pasterkamp, Gerard A1 - Peden, John F A1 - Peters, Annette A1 - Postma, Dirkje S A1 - Pramstaller, Peter P A1 - Price, Jackie F A1 - Qi, Lu A1 - Olli T Raitakari A1 - Rankinen, Tuomo A1 - Rao, D C A1 - Rice, Treva K A1 - Ridker, Paul M A1 - Rioux, John D A1 - Ritchie, Marylyn D A1 - Rudan, Igor A1 - Veikko Salomaa A1 - Nilesh J Samani A1 - Saramies, Jouko A1 - Sarzynski, Mark A A1 - Schunkert, Heribert A1 - Schwarz, Peter E H A1 - Peter Sever A1 - Alan R Shuldiner A1 - Sinisalo, Juha A1 - Stolk, Ronald P A1 - Strauch, Konstantin A1 - Tönjes, Anke A1 - Trégouët, David-Alexandre A1 - Tremblay, Angelo A1 - Tremoli, Elena A1 - Virtamo, Jarmo A1 - Vohl, Marie-Claude A1 - Völker, Uwe A1 - Waeber, Gérard A1 - Gonneke Willemsen A1 - Witteman, Jacqueline C A1 - Zillikens, M Carola A1 - Adair, Linda S A1 - Amouyel, Philippe A1 - Asselbergs, Folkert W A1 - Assimes, Themistocles L A1 - Bochud, Murielle A1 - Boehm, Bernhard O A1 - Boerwinkle, Eric A1 - Bornstein, Stefan R A1 - Erwin P Bottinger A1 - Bouchard, Claude A1 - Cauchi, Stéphane A1 - Chambers, John C A1 - Chanock, Stephen J A1 - Cooper, Richard S A1 - de Bakker, Paul I W A1 - George Dedoussis A1 - Luigi Ferrucci A1 - Franks, Paul W A1 - Froguel, Philippe A1 - Leif C Groop A1 - Christopher A Haiman A1 - Hamsten, Anders A1 - Hui, Jennie A1 - Hunter, David J A1 - Hveem, Kristian A1 - Kaplan, Robert C A1 - Mika Kivimäki A1 - Kuh, Diana A1 - Laakso, Markku A1 - Yongmei Liu A1 - Nicholas G Martin A1 - März, Winfried A1 - Melbye, Mads A1 - Andres Metspalu A1 - Moebus, Susanne A1 - Munroe, Patricia B A1 - Njølstad, Inger A1 - Ben A Oostra A1 - Palmer, Colin N A A1 - Nancy L Pedersen A1 - Markus Perola A1 - Pérusse, Louis A1 - Peters, Ulrike A1 - Power, Chris A1 - Quertermous, Thomas A1 - Rauramaa, Rainer A1 - Fernando Rivadeneira A1 - Saaristo, Timo E A1 - Saleheen, Danish A1 - Sattar, Naveed A1 - Eric E Schadt A1 - Schlessinger, David A1 - Eline P Slagboom A1 - Snieder, Harold A1 - Timothy Spector A1 - Thorsteinsdottir, Unnur A1 - Stumvoll, Michael A1 - Tuomilehto, Jaakko A1 - André G Uitterlinden A1 - Uusitupa, Matti A1 - van der Harst, Pim A1 - Walker, Mark A1 - Wallaschofski, Henri A1 - Wareham, Nicholas J A1 - Watkins, Hugh A1 - David R Weir A1 - Wichmann, H-Erich A1 - James F Wilson A1 - Zanen, Pieter A1 - Ingrid B Borecki A1 - Deloukas, Panos A1 - Caroline S Fox A1 - Iris M Heid A1 - Jeff O'Connell A1 - David P Strachan A1 - Stefansson, Kari A1 - Cornelia M van Duijn A1 - Gonçalo R Abecasis A1 - Lude L Franke A1 - Timothy M Frayling A1 - McCarthy, Mark I A1 - Peter M Visscher A1 - Scherag, Andre A1 - Willer, Cristen J A1 - Boehnke, Michael A1 - Mohlke, Karen L A1 - Lindgren, Cecilia M A1 - Beckmann, Jacques S A1 - Barroso, Inês A1 - Kari E North A1 - Ingelsson, Erik A1 - Joel N Hirschhron A1 - Ruth J F Loos A1 - Elizabeth K Speliotes KW - Age Factors KW - BMI KW - Continental Population Groups KW - Energy Metabolism KW - Europe KW - Female KW - Genome-Wide Association Study KW - Glutamic Acid KW - Humans KW - Insulin KW - Male KW - Obesity KW - Polymorphism, Single Nucleotide KW - Quantitative Trait Loci KW - Synapses AB -

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.

VL - 518 IS - 7538 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25673413?dopt=Abstract ER - TY - JOUR T1 - Genetic vulnerability to diabetes and obesity: does education offset the risk? JF - Soc Sci Med Y1 - 2015 A1 - Sze Y Liu A1 - Stefan Walter A1 - Jessica R Marden A1 - David Rehkopf A1 - Laura D Kubzansky A1 - Thu T Nguyen A1 - M. Maria Glymour KW - Aged KW - Body Mass Index KW - Diabetes Mellitus, Type 2 KW - Educational Status KW - European Continental Ancestry Group KW - Female KW - Genetic Predisposition to Disease KW - Genotype KW - Glycated Hemoglobin A KW - Health Status Disparities KW - Humans KW - Male KW - Middle Aged KW - Obesity KW - Risk Factors KW - Social determinants of health AB -

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.

VL - 127 UR - http://www.sciencedirect.com/science/article/pii/S0277953614005760 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25245452?dopt=Abstract ER - TY - JOUR T1 - Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples: Mendelian randomization analyses. JF - Alzheimers Dement Y1 - 2015 A1 - Mukherjee, Shubhabrata A1 - Stefan Walter A1 - Kauwe, John S K A1 - Andrew J Saykin A1 - David A Bennett A1 - Eric B Larson A1 - Paul K Crane A1 - M. Maria Glymour KW - Aged KW - Aged, 80 and over KW - Alzheimer disease KW - Body Mass Index KW - Female KW - Genotype KW - Humans KW - Linear Models KW - Male KW - Mendelian Randomization Analysis KW - Obesity KW - Phenotype KW - Polymorphism, Single Nucleotide KW - Risk Factors AB -

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.

VL - 11 IS - 12 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26079416?dopt=Abstract ER - TY - RPRT T1 - The Great Recession, Retirement and Related Outcomes Y1 - 2015 A1 - Alan L Gustman A1 - Thomas L. Steinmeier A1 - N. Tabatabai KW - Employment and Labor Force KW - Expectations KW - Public Policy AB - 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. PB - Cambridge, MA, National Bureau of Economic Research U4 - great Recession/labor Force Participation/Unemployment/expectations ER - TY - JOUR T1 - GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy. JF - J Gerontol A Biol Sci Med Sci Y1 - 2015 A1 - Broer, Linda A1 - Aron S Buchman A1 - Deelen, Joris A1 - Daniel S Evans A1 - Jessica Faul A1 - Kathryn L Lunetta A1 - Sebastiani, Paola A1 - Jennifer A Smith A1 - Albert Vernon Smith A1 - Toshiko Tanaka A1 - Lei Yu A1 - Alice M. Arnold A1 - Aspelund, Thor A1 - Emelia J Benjamin A1 - Philip L de Jager A1 - Guðny Eiríksdóttir A1 - Melissa E Garcia A1 - Hofman, Albert A1 - Kaplan, Robert C A1 - Sharon L R Kardia A1 - Douglas P Kiel A1 - Ben A Oostra A1 - Orwoll, Eric S A1 - Parimi, Neeta A1 - Psaty, Bruce M A1 - Fernando Rivadeneira A1 - Rotter, Jerome I A1 - Seshadri, Sudha A1 - Andrew B Singleton A1 - Henning Tiemeier A1 - André G Uitterlinden A1 - Wei Zhao A1 - Bandinelli, Stefania A1 - David A Bennett A1 - Luigi Ferrucci A1 - Gudnason, Vilmundur A1 - Tamara B Harris A1 - Karasik, David A1 - Lenore J Launer A1 - Thomas T Perls A1 - Eline P Slagboom A1 - Tranah, Gregory J A1 - David R Weir A1 - Anne B Newman A1 - Cornelia M van Duijn A1 - Joanne M Murabito KW - Aged KW - Aged, 80 and over KW - Apolipoproteins E KW - Cell Adhesion Molecules KW - Cohort Studies KW - Female KW - Forkhead Box Protein O3 KW - Forkhead Transcription Factors KW - Genome-Wide Association Study KW - Humans KW - Longevity KW - Male KW - Middle Aged KW - Polymorphism, Single Nucleotide KW - Receptors, Kainic Acid AB -

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.

VL - 70 UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296168/ IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25199915?dopt=Abstract ER - TY - JOUR T1 - Genetic diversity is a predictor of mortality in humans. JF - BMC Genet Y1 - 2014 A1 - Bihlmeyer, Nathan A A1 - Brody, Jennifer A A1 - Albert Vernon Smith A1 - Kathryn L Lunetta A1 - Michael A Nalls A1 - Jennifer A Smith A1 - Toshiko Tanaka A1 - Gail Davies A1 - Lei Yu A1 - Saira S Mirza A1 - Teumer, Alexander A1 - Coresh, Josef A1 - Pankow, James S A1 - Franceschini, Nora A1 - Scaria, Anish A1 - Oshima, Junko A1 - Psaty, Bruce M A1 - Gudnason, Vilmundur A1 - Guðny Eiríksdóttir A1 - Tamara B Harris A1 - Li, Hanyue A1 - Karasik, David A1 - Douglas P Kiel A1 - Melissa E Garcia A1 - Yongmei Liu A1 - Jessica Faul A1 - Sharon L R Kardia A1 - Wei Zhao A1 - Luigi Ferrucci A1 - Allerhand, Michael A1 - David C Liewald A1 - Redmond, Paul A1 - John M Starr A1 - Philip L de Jager A1 - Nese Direk A1 - Mohammed Arfan Ikram A1 - André G Uitterlinden A1 - Homuth, Georg A1 - Lorbeer, Roberto A1 - Hans-Jörgen Grabe A1 - Lenore J Launer A1 - Joanne M Murabito A1 - Andrew B Singleton A1 - David R Weir A1 - Bandinelli, Stefania A1 - Ian J Deary A1 - David A Bennett A1 - Henning Tiemeier A1 - Kocher, Thomas A1 - Lumley, Thomas A1 - Dan E Arking KW - Genome-Wide Association Study KW - Heterozygote KW - Humans KW - Mortality KW - Polymorphism, Single Nucleotide KW - Proportional Hazards Models AB -

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.

VL - 15 UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4301661/ U1 - http://www.ncbi.nlm.nih.gov/pubmed/25543667?dopt=Abstract ER - TY - JOUR T1 - Genomic assortative mating in marriages in the United States. JF - PLoS One Y1 - 2014 A1 - Guo, Guang A1 - Wang, Lin A1 - Hexuan Liu A1 - Randall, Thomas KW - Data collection KW - Female KW - Genome, Human KW - Genomics KW - Genotype KW - Humans KW - Male KW - Marriage KW - Middle Aged KW - Phenotype KW - Polymorphism, Single Nucleotide KW - Reproduction KW - United States AB -

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.

VL - 9 IS - 11 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25384046?dopt=Abstract ER - TY - RPRT T1 - The Great Recession, Decline and Rebound in Household Wealth for the Near Retirement Population Y1 - 2014 A1 - Alan L Gustman A1 - Thomas L. Steinmeier A1 - N. Tabatabai KW - Health Conditions and Status KW - Net Worth and Assets KW - Public Policy AB - 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. PB - Cambridge, MA, National Bureau of Economic Research U4 - great Recession/Asset accumulation/household wealth/asset values/loss recovery ER - TY - JOUR T1 - A Genetic IV Analysis to Assess the Effect of Body Mass Index on Depression in the Health And Retirement Study JF - Am J Epidemiol Y1 - 2013 A1 - Stefan Walter A1 - Mejía-Guevara, Iván A1 - Eric J. Tchetgen Tchetgen A1 - Karestan C Koenen A1 - Ichiro Kawachi A1 - Laura D Kubzansky A1 - M. Maria Glymour KW - Genetics KW - Health Conditions and Status KW - Public Policy AB - 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. PB - 177 VL - 177 U4 - public Health/occupational health/Body Mass Index/Genetic Markers/risk alleles/genetic risk score/Depression/biological pathways/mental Health/genetics/genetics ER - TY - JOUR T1 - Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations. JF - Am J Hum Genet Y1 - 2013 A1 - Franceschini, Nora A1 - Fox, Ervin A1 - Zhang, Zhaogong A1 - Edwards, Todd L A1 - Michael A Nalls A1 - Yun Ju Sung A1 - Bamidele O Tayo A1 - Yan V Sun A1 - Gottesman, Omri A1 - Adebawole Adeyemo A1 - Andrew D Johnson A1 - Young, J Hunter A1 - Kenneth Rice A1 - Duan, Qing A1 - Chen, Fang A1 - Yun Li A1 - Tang, Hua A1 - Myriam Fornage A1 - Keene, Keith L A1 - Andrews, Jeanette S A1 - Jennifer A Smith A1 - Jessica Faul A1 - Guangfa, Zhang A1 - Guo, Wei A1 - Liu, Yu A1 - Murray, Sarah S A1 - Musani, Solomon K A1 - Srinivasan, Sathanur A1 - Digna R Velez Edwards A1 - Wang, Heming A1 - Becker, Lewis C A1 - Bovet, Pascal A1 - Bochud, Murielle A1 - Broeckel, Ulrich A1 - Burnier, Michel A1 - Carty, Cara A1 - Daniel I Chasman A1 - Georg B Ehret A1 - Chen, Wei-Min A1 - Chen, Guanjie A1 - Wei Chen A1 - Ding, Jingzhong A1 - Dreisbach, Albert W A1 - Michele K Evans A1 - Guo, Xiuqing A1 - Melissa E Garcia A1 - Jensen, Rich A1 - Keller, Margaux F A1 - Lettre, Guillaume A1 - Lotay, Vaneet A1 - Martin, Lisa W A1 - Moore, Jason H A1 - Alanna C Morrison A1 - Thomas H Mosley A1 - Ogunniyi, Adesola A1 - Walter R Palmas A1 - George J Papanicolaou A1 - Alan Penman A1 - Polak, Joseph F A1 - Ridker, Paul M A1 - Babatunde Salako A1 - Andrew B Singleton A1 - Daniel Shriner A1 - Kent D Taylor A1 - Ramachandran S Vasan A1 - Kerri Wiggins A1 - Williams, Scott M A1 - Yanek, Lisa R A1 - Wei Zhao A1 - Alan B Zonderman A1 - Becker, Diane M A1 - Berenson, Gerald A1 - Boerwinkle, Eric A1 - Erwin P Bottinger A1 - Cushman, Mary A1 - Charles B Eaton A1 - Nyberg, Fredrik A1 - Gerardo Heiss A1 - Joel N Hirschhron A1 - Howard, Virginia J A1 - Karczewsk, Konrad J A1 - Lanktree, Matthew B A1 - Liu, Kiang A1 - Yongmei Liu A1 - Ruth J F Loos A1 - Margolis, Karen A1 - Snyder, Michael A1 - Psaty, Bruce M A1 - Schork, Nicholas J A1 - David R Weir A1 - Charles N Rotimi A1 - Sale, Michele M A1 - Tamara B Harris A1 - Sharon L R Kardia A1 - Hunt, Steven C A1 - Donna K Arnett A1 - Redline, Susan A1 - Cooper, Richard S A1 - Neil Risch A1 - Rao, D C A1 - Rotter, Jerome I A1 - Chakravarti, Aravinda A1 - Reiner, Alex P A1 - Levy, Daniel A1 - Keating, Brendan J A1 - Zhu, Xiaofeng KW - Africa KW - African Continental Ancestry Group KW - Blood pressure KW - Cohort Studies KW - Databases, Genetic KW - Genetic Loci KW - Genetic Predisposition to Disease KW - Genome-Wide Association Study KW - Humans KW - Polymorphism, Single Nucleotide KW - Quantitative Trait, Heritable KW - Reproducibility of Results AB -

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.

VL - 93 IS - 3 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23972371?dopt=Abstract ER - TY - JOUR T1 - GWAS of 126,559 individuals identifies genetic variants associated with educational attainment. JF - Science Y1 - 2013 A1 - Cornelius A Rietveld A1 - Sarah E Medland A1 - Derringer, Jaime A1 - Yang, Jian A1 - Tõnu Esko A1 - Martin, Nicolas W A1 - Westra, Harm-Jan A1 - Shakhbazov, Konstantin A1 - Abdel Abdellaoui A1 - Agrawal, Arpana A1 - Albrecht, Eva A1 - Alizadeh, Behrooz Z A1 - Amin, Najaf A1 - Barnard, John A1 - Baumeister, Sebastian E A1 - Benke, Kelly S A1 - Bielak, Lawrence F A1 - Boatman, Jeffrey A A1 - Patricia A. Boyle A1 - Gail Davies A1 - Christiaan de Leeuw A1 - Eklund, Niina A1 - Daniel S Evans A1 - Rudolf Ferhmann A1 - Fischer, Krista A1 - Gieger, Christian A1 - Gjessing, Håkon K A1 - Hägg, Sara A1 - Harris, Jennifer R A1 - Caroline Hayward A1 - Holzapfel, Christina A1 - Carla A Ibrahim-Verbaas A1 - Ingelsson, Erik A1 - Jacobsson, Bo A1 - Joshi, Peter K A1 - Jugessur, Astanand A1 - Marika A Kaakinen A1 - Kanoni, Stavroula A1 - Karjalainen, Juha A1 - Kolcic, Ivana A1 - Kristiansson, Kati A1 - Kutalik, Zoltán A1 - J. Lahti A1 - Lee, Sang H A1 - Lin, Peng A1 - Penelope A Lind A1 - Yongmei Liu A1 - Kurt Lohman A1 - Loitfelder, Marisa A1 - McMahon, George A1 - Vidal, Pedro Marques A1 - Osorio Meirelles A1 - Lili Milani A1 - Myhre, Ronny A1 - Nuotio, Marja-Liisa A1 - Christopher J Oldmeadow A1 - Katja E Petrovic A1 - Wouter J Peyrot A1 - Polasek, Ozren A1 - Quaye, Lydia A1 - Reinmaa, Eva A1 - Rice, John P A1 - Rizzi, Thais S A1 - Schmidt, Helena A1 - Schmidt, Reinhold A1 - Albert Vernon Smith A1 - Jennifer A Smith A1 - Toshiko Tanaka A1 - Antonio Terracciano A1 - van der Loos, Matthijs J H M A1 - Vitart, Veronique A1 - Völzke, Henry A1 - Jürgen Wellmann A1 - Lei Yu A1 - Wei Zhao A1 - Allik, Jüri A1 - John R. Attia A1 - Bandinelli, Stefania A1 - Bastardot, François A1 - Jonathan P. Beauchamp A1 - David A Bennett A1 - Klaus Berger A1 - Laura Bierut A1 - Dorret I Boomsma A1 - Bültmann, Ute A1 - Campbell, Harry A1 - Chabris, Christopher F A1 - Cherkas, Lynn A1 - Chung, Mina K A1 - Francesco Cucca A1 - de Andrade, Mariza A1 - Philip L de Jager A1 - De Neve, Jan-Emmanuel A1 - Ian J Deary A1 - George Dedoussis A1 - Deloukas, Panos A1 - Dimitriou, Maria A1 - Guðny Eiríksdóttir A1 - Elderson, Martin F A1 - Johan G Eriksson A1 - Jessica Faul A1 - Luigi Ferrucci A1 - Melissa E Garcia A1 - Grönberg, Henrik A1 - Guðnason, Vilmundur A1 - Hall, Per A1 - Harris, Juliette M A1 - Tamara B Harris A1 - Nicholas D Hastie A1 - Andrew C Heath A1 - Dena G Hernandez A1 - Hoffmann, Wolfgang A1 - Hofman, Adriaan A1 - Holle, Rolf A1 - Holliday, Elizabeth G A1 - Jouke-Jan Hottenga A1 - Iacono, William G A1 - Illig, Thomas A1 - Järvelin, Marjo-Riitta A1 - Kähönen, Mika A1 - Kaprio, Jaakko A1 - Kirkpatrick, Robert M A1 - Kowgier, Matthew A1 - Latvala, Antti A1 - Lenore J Launer A1 - Lawlor, Debbie A A1 - Lehtimäki, Terho A1 - Li, Jingmei A1 - Paul Lichtenstein A1 - Lichtner, Peter A1 - David C Liewald A1 - Pamela A F Madden A1 - Patrik K E Magnusson A1 - Mäkinen, Tomi E A1 - Masala, Marco A1 - McGue, Matt A1 - Andres Metspalu A1 - Mielck, Andreas A1 - Michael B Miller A1 - Grant W Montgomery A1 - Mukherjee, Sutapa A1 - Nyholt, Dale R A1 - Ben A Oostra A1 - Palmer, Lyle J A1 - Aarno Palotie A1 - Brenda W J H Penninx A1 - Markus Perola A1 - Peyser, Patricia A A1 - Preisig, Martin A1 - Katri Räikkönen A1 - Olli T Raitakari A1 - Realo, Anu A1 - Ring, Susan M A1 - Ripatti, Samuli A1 - Fernando Rivadeneira A1 - Rudan, Igor A1 - Rustichini, Aldo A1 - Veikko Salomaa A1 - Sarin, Antti-Pekka A1 - Schlessinger, David A1 - Rodney J Scott A1 - Snieder, Harold A1 - St Pourcain, Beate A1 - John M Starr A1 - Sul, Jae Hoon A1 - Surakka, Ida A1 - Svento, Rauli A1 - Teumer, Alexander A1 - Henning Tiemeier A1 - van Rooij, Frank J A A1 - Van Wagoner, David R A1 - Vartiainen, Erkki A1 - Viikari, Jorma A1 - Vollenweider, Peter A1 - Vonk, Judith M A1 - Waeber, Gérard A1 - David R Weir A1 - Wichmann, H-Erich A1 - Elisabeth Widen A1 - Gonneke Willemsen A1 - James F Wilson A1 - Alan F Wright A1 - Dalton C Conley A1 - Davey-Smith, George A1 - Lude L Franke A1 - Groenen, Patrick J F A1 - Hofman, Albert A1 - Johannesson, Magnus A1 - Sharon L R Kardia A1 - Krueger, Robert F A1 - David I Laibson A1 - Nicholas G Martin A1 - Meyer, Michelle N A1 - Posthuma, Danielle A1 - A. Roy Thurik A1 - Nicholas J Timpson A1 - André G Uitterlinden A1 - Cornelia M van Duijn A1 - Peter M Visscher A1 - Daniel J. Benjamin A1 - Cesarini, David A1 - Philipp D Koellinger KW - Cognition KW - Educational Status KW - Endophenotypes KW - Female KW - Genetic Loci KW - Genome-Wide Association Study KW - Humans KW - Male KW - Multifactorial Inheritance KW - Polymorphism, Single Nucleotide AB -

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.

VL - 340 IS - 6139 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23722424?dopt=Abstract ER - TY - JOUR T1 - The growth in Social Security benefits among the retirement-age population from increases in the cap on covered earnings. JF - Soc Secur Bull Y1 - 2012 A1 - Alan L Gustman A1 - Thomas L. Steinmeier A1 - N. Tabatabai KW - Aged KW - Cohort Studies KW - Female KW - Humans KW - Insurance Benefits KW - Male KW - Middle Aged KW - Models, Econometric KW - Public Policy KW - Salaries and Fringe Benefits KW - Social Security KW - Taxes KW - United States AB -

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.

PB - 72 VL - 72 UR - https://www.ssa.gov/policy/docs/ssb/v72n2/v72n2p49.html IS - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/22799138?dopt=Abstract U4 - Social security/payroll tax/Public policy/retirement planning/taxation ER - TY - RPRT T1 - The Growth in Social Security Benefits Among the Retirement Age Population from Increases in the Cap on Covered Earnings Y1 - 2010 A1 - Alan L Gustman A1 - Thomas L. Steinmeier A1 - Tabatabai, Nahid KW - Demographics KW - Public Policy KW - Social Security AB - 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. JF - NBER Working Paper PB - National Bureau of Economic Research CY - Cambridge, MA U4 - social Security/early boomers/earnings and Benefits File/Public Policy/payroll tax/tax revenues ER -