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 - Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits. JF - Human Genetics and Genomics Advances Y1 - 2021 A1 - Sun, Daokun A1 - Melissa Richard A1 - Musani, Solomon K A1 - Yun Ju Sung A1 - Thomas W Winkler A1 - Schwander, Karen A1 - Jin-Fang Chai A1 - Guo, Xiuqing A1 - Kilpeläinen, Tuomas O A1 - Vojinovic, Dina A1 - Aschard, Hugues A1 - Traci M Bartz A1 - Bielak, Lawrence F A1 - Brown, Michael R A1 - Chitrala, Kumaraswamy A1 - Hartwig, Fernando P A1 - Horimoto, Andrea R V R A1 - Liu, Yongmei A1 - Alisa Manning A1 - Noordam, Raymond A1 - Smith, Albert V A1 - Sarah E Harris A1 - Kühnel, Brigitte A1 - Lyytikäinen, Leo-Pekka A1 - Ilja M Nolte A1 - Rauramaa, Rainer A1 - van der Most, Peter J A1 - Wang, Rujia A1 - Erin B Ware A1 - Weiss, Stefan A1 - Wen, Wanqing A1 - Yanek, Lisa R A1 - Dan E Arking A1 - Donna K Arnett A1 - Barac, Ana A1 - Boerwinkle, Eric A1 - Broeckel, Ulrich A1 - Chakravarti, Aravinda A1 - Chen, Yii-Der Ida A1 - Cupples, L Adrienne A1 - Davigulus, Martha L A1 - de Las Fuentes, Lisa A1 - de Mutsert, Renée A1 - de Vries, Paul S A1 - Delaney, Joseph A C A1 - Ana V Diez Roux A1 - Dörr, Marcus A1 - Jessica Faul A1 - Fretts, Amanda M A1 - Gallo, Linda C A1 - Hans-Jörgen Grabe A1 - Gu, C Charles A1 - Tamara B Harris A1 - Hartman, Catharina C A A1 - Heikkinen, Sami A1 - Ikram, M Arfan A1 - Isasi, Carmen A1 - Johnson, W Craig A1 - Jost Bruno Jonas A1 - Kaplan, Robert C A1 - Komulainen, Pirjo A1 - Krieger, Jose E A1 - Levy, Daniel A1 - Liu, Jianjun A1 - Kurt Lohman A1 - Luik, Annemarie I A1 - Martin, Lisa W A1 - Meitinger, Thomas A1 - Milaneschi, Yuri A1 - Jeff O'Connell A1 - Walter R Palmas A1 - Peters, Annette A1 - Peyser, Patricia A A1 - Pulkki-Raback, Laura A1 - Raffel, Leslie J A1 - Reiner, Alex P A1 - Kenneth Rice A1 - Robinson, Jennifer G A1 - Rosendaal, Frits R A1 - Schmidt, Carsten Oliver A1 - Schreiner, Pamela J A1 - Schwettmann, Lars A1 - Shikany, James M A1 - Shu, Xiao-Ou A1 - Stephen Sidney A1 - Sims, Mario A1 - Smith, Jennifer A A1 - Sotoodehnia, Nona A1 - Strauch, Konstantin A1 - Tai, E Shyong A1 - Taylor, Kent A1 - André G Uitterlinden A1 - Cornelia M van Duijn A1 - Waldenberger, Melanie A1 - Wee, Hwee-Lin A1 - Wei, Wen-Bin A1 - Wilson, Gregory A1 - Xuan, Deng A1 - Yao, Jie A1 - Zeng, Donglin A1 - Zhao, Wei A1 - Zhu, Xiaofeng A1 - Alan B Zonderman A1 - Becker, Diane M A1 - Ian J Deary A1 - Gieger, Christian A1 - Lakka, Timo A A1 - Lehtimäki, Terho A1 - Kari E North A1 - Oldehinkel, Albertine J A1 - Brenda W J H Penninx A1 - Snieder, Harold A1 - Wang, Ya-Xing A1 - David R Weir A1 - Zheng, Wei A1 - Michele K Evans A1 - Gauderman, W James A1 - Gudnason, Vilmundur A1 - Horta, Bernardo L A1 - Liu, Ching-Ti A1 - Dennis O Mook-Kanamori A1 - Alanna C Morrison A1 - Pereira, Alexandre C A1 - Psaty, Bruce M A1 - Amin, Najaf A1 - Fox, Ervin R A1 - Charles Kooperberg A1 - Sim, Xueling A1 - Laura Bierut A1 - Rotter, Jerome I A1 - Sharon L R Kardia A1 - Franceschini, Nora A1 - Rao, Dabeeru C A1 - Myriam Fornage KW - blood pressure traits AB -

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

VL - 2 IS - 1 ER - TY - JOUR T1 - Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity. JF - Nature Communications Y1 - 2019 A1 - Kilpeläinen, Tuomas O A1 - Bentley, Amy R A1 - Noordam, Raymond A1 - Yun Ju Sung A1 - Schwander, Karen A1 - Thomas W Winkler A1 - Jakupović, Hermina A1 - Daniel I Chasman A1 - Alisa Manning A1 - Ntalla, Ioanna A1 - Aschard, Hugues A1 - Brown, Michael R A1 - de Las Fuentes, Lisa A1 - Franceschini, Nora A1 - Guo, Xiuqing A1 - Vojinovic, Dina A1 - Aslibekyan, Stella A1 - Feitosa, Mary F A1 - Kho, Minjung A1 - Musani, Solomon K A1 - Melissa Richard A1 - Wang, Heming A1 - Wang, Zhe A1 - Traci M Bartz A1 - Bielak, Lawrence F A1 - Campbell, Archie A1 - Dorajoo, Rajkumar A1 - Fisher, Virginia A1 - Hartwig, Fernando P A1 - Horimoto, Andrea R V R A1 - Li, Changwei A1 - Kurt Lohman A1 - Marten, Jonathan A1 - Sim, Xueling A1 - Smith, Albert V A1 - Tajuddin, Salman M A1 - Alver, Maris A1 - Amini, Marzyeh A1 - Boissel, Mathilde A1 - Jin-Fang Chai A1 - Chen, Xu A1 - Divers, Jasmin A1 - Evangelou, Evangelos A1 - Gao, Chuan A1 - Graff, Mariaelisa A1 - Sarah E Harris A1 - He, Meian A1 - Hsu, Fang-Chi A1 - Jackson, Anne U A1 - Jing Hua Zhao A1 - Kraja, Aldi T A1 - Kühnel, Brigitte A1 - Laguzzi, Federica A1 - Lyytikäinen, Leo-Pekka A1 - Ilja M Nolte A1 - Rauramaa, Rainer A1 - Riaz, Muhammad A1 - Robino, Antonietta A1 - Rueedi, Rico A1 - Heather M Stringham A1 - Takeuchi, Fumihiko A1 - van der Most, Peter J A1 - Varga, Tibor V A1 - Verweij, Niek A1 - Erin B Ware A1 - Wen, Wanqing A1 - Li, Xiaoyin A1 - Yanek, Lisa R A1 - Amin, Najaf A1 - Donna K Arnett A1 - Boerwinkle, Eric A1 - Brumat, Marco A1 - Brian E Cade A1 - Canouil, Mickaël A1 - Chen, Yii-Der Ida A1 - Concas, Maria Pina A1 - Connell, John A1 - de Mutsert, Renée A1 - de Silva, H Janaka A1 - de Vries, Paul S A1 - Demirkan, Ayse A1 - Ding, Jingzhong A1 - Charles B Eaton A1 - Jessica Faul A1 - Friedlander, Yechiel A1 - Gabriel, Kelley P A1 - Ghanbari, Mohsen 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 C A1 - Ikram, M Arfan A1 - Jost Bruno Jonas A1 - Koh, Woon-Puay A1 - Komulainen, Pirjo A1 - Krieger, Jose E A1 - Stephen B Kritchevsky A1 - Kutalik, Zoltán A1 - Kuusisto, Johanna A1 - Langefeld, Carl D A1 - Langenberg, Claudia A1 - Lenore J Launer A1 - Leander, Karin A1 - Lemaitre, Rozenn N A1 - Lewis, Cora E A1 - Liang, Jingjing A1 - Liu, Jianjun A1 - Mägi, Reedik A1 - Manichaikul, Ani A1 - Meitinger, Thomas A1 - Andres Metspalu A1 - Milaneschi, Yuri A1 - Mohlke, Karen L A1 - Thomas H Mosley A1 - Murray, Alison D A1 - Michael A Nalls A1 - Nang, Ei-Ei Khaing A1 - Nelson, Christopher P A1 - Nona, Sotoodehnia A1 - Norris, Jill M A1 - Nwuba, Chiamaka Vivian A1 - Jeff O'Connell A1 - Palmer, Nicholette D A1 - Papanicolau, George J A1 - Pazoki, Raha A1 - Nancy L Pedersen A1 - Peters, Annette A1 - Peyser, Patricia A A1 - Polasek, Ozren A1 - David J Porteous A1 - Poveda, Alaitz A1 - Olli T Raitakari A1 - Rich, Stephen S A1 - Neil Risch A1 - Robinson, Jennifer G A1 - Rose, Lynda M A1 - Rudan, Igor A1 - Schreiner, Pamela J A1 - Scott, Robert A A1 - Stephen Sidney A1 - Sims, Mario A1 - Smith, Jennifer A A1 - Snieder, Harold A1 - Sofer, Tamar A1 - John M Starr A1 - Sternfeld, Barbara A1 - Strauch, Konstantin A1 - Tang, Hua A1 - Kent D Taylor A1 - Tsai, Michael Y A1 - Tuomilehto, Jaakko A1 - André G Uitterlinden A1 - van der Ende, M Yldau A1 - van Heemst, Diana A1 - Voortman, Trudy A1 - Waldenberger, Melanie A1 - Wennberg, Patrik A1 - Wilson, Gregory A1 - Xiang, Yong-Bing A1 - Yao, Jie A1 - Yu, Caizheng A1 - Yuan, Jian-Min A1 - Zhao, Wei A1 - Alan B Zonderman A1 - Becker, Diane M A1 - Boehnke, Michael A1 - Bowden, Donald W A1 - de Faire, Ulf A1 - Ian J Deary A1 - Elliott, Paul A1 - Tõnu Esko A1 - Freedman, Barry I A1 - Froguel, Philippe A1 - Paolo P. Gasparini A1 - Gieger, Christian A1 - Kato, Norihiro A1 - Laakso, Markku A1 - Lakka, Timo A A1 - Lehtimäki, Terho A1 - Patrik K E Magnusson A1 - Oldehinkel, Albertine J A1 - Brenda W J H Penninx A1 - Nilesh J Samani A1 - Shu, Xiao-Ou A1 - van der Harst, Pim A1 - Jana V. van Vliet-Ostaptchouk A1 - Vollenweider, Peter A1 - Wagenknecht, Lynne E A1 - Wang, Ya X A1 - Wareham, Nicholas J A1 - David R Weir A1 - Wu, Tangchun A1 - Zheng, Wei A1 - Zhu, Xiaofeng A1 - Michele K Evans A1 - Franks, Paul W A1 - Gudnason, Vilmundur A1 - Caroline Hayward A1 - Horta, Bernardo L A1 - Tanika N Kelly A1 - Liu, Yongmei A1 - Kari E North A1 - Pereira, Alexandre C A1 - Ridker, Paul M A1 - Tai, E Shyong A1 - van Dam, Rob M A1 - Fox, Ervin R A1 - Sharon L R Kardia A1 - Liu, Ching-Ti A1 - Dennis O Mook-Kanamori A1 - Province, Michael A A1 - Redline, Susan A1 - Cornelia M van Duijn A1 - Rotter, Jerome I A1 - Charles Kooperberg A1 - Gauderman, W James A1 - Psaty, Bruce M A1 - Kenneth Rice A1 - Munroe, Patricia B A1 - Myriam Fornage A1 - Cupples, L Adrienne A1 - Charles N Rotimi A1 - Alanna C Morrison A1 - Rao, Dabeeru C A1 - Ruth J F Loos KW - Adolescent KW - Adult KW - Aged KW - Aged, 80 and over KW - Asians KW - Blacks KW - Brazil KW - Calcium-Binding Proteins KW - Cholesterol KW - Cholesterol, HDL KW - Cholesterol, LDL KW - Exercise KW - Female KW - Genetic Loci KW - Genome-Wide Association Study KW - Genotype KW - Hispanic or Latino KW - Humans KW - LIM-Homeodomain Proteins KW - Lipid Metabolism KW - Lipids KW - Male KW - Membrane Proteins KW - Microtubule-Associated Proteins KW - Middle Aged KW - Muscle Proteins KW - Nerve Tissue Proteins KW - Transcription Factors KW - Triglycerides KW - Whites KW - Young Adult AB -

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

VL - 10 IS - 1 ER - TY - JOUR T1 - New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders. JF - Nature Human Behaviour Y1 - 2019 A1 - Evangelou, Evangelos A1 - Gao, He A1 - Chu, Congying A1 - Ntritsos, Georgios A1 - Blakeley, Paul A1 - Butts, Andrew R A1 - Pazoki, Raha A1 - Suzuki, Hideaki A1 - Koskeridis, Fotios A1 - Yiorkas, Andrianos M A1 - Karaman, Ibrahim A1 - Elliott, Joshua A1 - Luo, Qiang A1 - Aeschbacher, Stefanie A1 - Traci M Bartz A1 - Baumeister, Sebastian E A1 - Braund, Peter S A1 - Brown, Michael R A1 - Brody, Jennifer A A1 - Clarke, Toni-Kim A1 - Dimou, Niki A1 - Jessica Faul A1 - Homuth, Georg A1 - Jackson, Anne U A1 - Kentistou, Katherine A A1 - Joshi, Peter K A1 - Lemaitre, Rozenn N A1 - Penelope A Lind A1 - Lyytikäinen, Leo-Pekka A1 - Mangino, Massimo A1 - Milaneschi, Yuri A1 - Nelson, Christopher P A1 - Ilja M Nolte A1 - Perälä, Mia-Maria A1 - Polasek, Ozren A1 - David J Porteous A1 - Scott M Ratliff A1 - Smith, Jennifer A A1 - Stančáková, Alena A1 - Teumer, Alexander A1 - Tuominen, Samuli A1 - Thériault, Sébastien A1 - Vangipurapu, Jagadish A1 - Whitfield, John B A1 - Wood, Alexis A1 - Yao, Jie A1 - Yu, Bing A1 - Zhao, Wei A1 - Dan E Arking A1 - Auvinen, Juha A1 - Liu, Chunyu A1 - Männikkö, Minna A1 - Risch, Lorenz A1 - Rotter, Jerome I A1 - Snieder, Harold A1 - Veijola, Juha A1 - Alexandra I Blakemore A1 - Boehnke, Michael A1 - Campbell, Harry A1 - Conen, David A1 - Johan G Eriksson A1 - Hans-Jörgen Grabe A1 - Guo, Xiuqing A1 - van der Harst, Pim A1 - Catharina A Hartman A1 - Caroline Hayward A1 - Andrew C Heath A1 - Järvelin, Marjo-Riitta A1 - Kähönen, Mika A1 - Sharon L R Kardia A1 - Kühne, Michael A1 - Kuusisto, Johanna A1 - Laakso, Markku A1 - Lahti, Jari A1 - Lehtimäki, Terho A1 - McIntosh, Andrew M A1 - Mohlke, Karen L A1 - Alanna C Morrison A1 - Nicholas G Martin A1 - Oldehinkel, Albertine J A1 - Brenda W J H Penninx A1 - Psaty, Bruce M A1 - Olli T Raitakari A1 - Rudan, Igor A1 - Nilesh J Samani A1 - Scott, Laura J A1 - Timothy Spector A1 - Verweij, Niek A1 - David R Weir A1 - James F Wilson A1 - Levy, Daniel A1 - Tzoulaki, Ioanna A1 - Bell, Jimmy D A1 - Matthews, Paul M A1 - Rothenfluh, Adrian A1 - Desrivières, Sylvane A1 - Schumann, Gunter A1 - Elliott, Paul KW - Adult KW - Aged KW - Alcohol Drinking KW - Alcoholism KW - Brain KW - Female KW - genes KW - Genetic Predisposition to Disease KW - Genome-Wide Association Study KW - Humans KW - Magnetic Resonance Imaging KW - Male KW - Mental Disorders KW - Middle Aged KW - Neuroimaging KW - Polymorphism, Single Nucleotide KW - Quantitative Trait Loci KW - Schizophrenia KW - Whites AB -

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

VL - 3 IS - 9 ER - TY - JOUR T1 - Using Polygenic Scores in Social Science Research: Unraveling Childlessness JF - Frontiers in Sociology Y1 - 2019 A1 - Verweij, Renske M. A1 - Melinda C Mills A1 - Stulp, Gert A1 - Ilja M Nolte A1 - Nicola Barban A1 - Felix C Tropf A1 - Carrell, Douglas T. A1 - Aston, Kenneth I. A1 - Krina T Zondervan A1 - Rahmioglu, Nilufer A1 - Dalgaard, Marlene A1 - Skaarup, Carina A1 - Hayes, M. Geoffrey A1 - Dunaif, Andrea A1 - Guo, Guang A1 - Snieder, Harold KW - childlessness KW - polygenic score KW - social science AB - Biological, genetic, and socio-demographic factors are all important in explaining reproductive behavior, yet these factors are typically studied in isolation. In this study, we explore an innovative sociogenomic approach, which entails including key socio-demographic (marriage, education, occupation, religion, cohort) and genetic factors related to both behavioral [age at first birth (AFB), number of children ever born (NEB)] and biological fecundity-related outcomes (endometriosis, age at menopause and menarche, polycystic ovary syndrome, azoospermia, testicular dysgenesis syndrome) to explain childlessness. We examine the association of all sets of factors with childlessness as well as the interplay between them. We derive polygenic scores (PGS) from recent genome-wide association studies (GWAS) and apply these in the Health and Retirement Study (N = 10,686) and Wisconsin Longitudinal Study (N = 8,284). Both socio-demographic and genetic factors were associated with childlessness. Whilst socio-demographic factors explain 19–46% in childlessness, the current PGS explains <1% of the variance, and only PGSs from large GWASs are related to childlessness. Our findings also indicate that genetic and socio-demographic factors are not independent, with PGSs for AFB and NEB related to education and age at marriage. The explained variance by polygenic scores on childlessness is limited since it is largely a behavioral trait, with genetic explanations expected to increase somewhat in the future with better-powered GWASs. As genotyping of individuals in social science surveys becomes more prevalent, the method described in this study can be applied to other outcomes. VL - 4 UR - https://www.frontiersin.org/article/10.3389/fsoc.2019.00074 ER - TY - JOUR T1 - Genotype–covariate interaction effects and the heritability of adult body mass index JF - Nature Genetics Y1 - 2017 A1 - Matthew R Robinson A1 - English, Geoffrey A1 - Moser, Gerhard A1 - Lloyd-Jones, Luke R. A1 - Triplett, Marcus A. A1 - Zhihong Zhu A1 - Ilja M Nolte A1 - Jana V. van Vliet-Ostaptchouk A1 - Snieder, Harold A1 - Tõnu Esko A1 - Lili Milani A1 - Mägi, Reedik A1 - Andres Metspalu A1 - Patrik K E Magnusson A1 - Nancy L Pedersen A1 - Ingelsson, Erik A1 - Johannesson, Magnus A1 - Yang, Jian A1 - Cesarini, David A1 - Peter M Visscher KW - BMI KW - Genetics KW - GWAS AB - Obesity is a worldwide epidemie, with major health and economic costs. Here we estimate heritability for body mass index (BMI) in 172,000 sibling pairs and 150,832 unrelated individuals and explore the contribution of genotype-covariate interaction effects at common SNP loci. We find evidence for genotype-age interaction (likelihood ratio test (LRT) = 73.58, degrees of freedom (df) = 1, P = 4.83 x 10-18), which contributed 8.1 % (1.4% s.e.) to BMI variation. Across eight self-reported lifestyle factors, including diet and exercise, we find genotype-environment interaction only for smoking behavior (LRT = 19.70, P = 5.03 x 10-5 and LRT = 30.80, P = 1.42 x 10-8), which contributed 4.0% (0.8% s.e.) to BMI variation. Bayesian association analysis suggests that BMI is highly polygenic, with 75% of the SNP heritability attributable to loci that each explain <0.01 % of the phenotypic variance. Our findings imply that substantially larger sample sizes across ages and lifestyles are required to understand the full genetic architecture of BMI. VL - 49 IS - 8 JO - Nat Genet 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 - Personality Polygenes, Positive Affect, and Life Satisfaction. JF - Twin Res Hum Genet Y1 - 2016 A1 - Weiss, Alexander A1 - Baselmans, Bart M L A1 - Edith Hofer A1 - Yang, Jingyun A1 - Okbay, Aysu A1 - Penelope A Lind A1 - Michael B Miller A1 - Ilja M Nolte A1 - Wei Zhao A1 - Hagenaars, Saskia P A1 - Jouke-Jan Hottenga A1 - Lindsay K Matteson A1 - Snieder, Harold A1 - Jessica Faul A1 - Catharina A Hartman A1 - Patricia A. Boyle A1 - Henning Tiemeier A1 - Mosing, Miriam A A1 - Pattie, Alison A1 - Gail Davies A1 - David C Liewald A1 - Schmidt, Reinhold A1 - Philip L de Jager A1 - Andrew C Heath A1 - Markus Jokela A1 - John M Starr A1 - Oldehinkel, Albertine J A1 - Johannesson, Magnus A1 - Cesarini, David A1 - Hofman, Albert A1 - Sarah E Harris A1 - Jennifer A Smith A1 - Keltikangas-Järvinen, Liisa A1 - Pulkki-Raback, Laura A1 - Schmidt, Helena A1 - Jacqui Smith A1 - Iacono, William G A1 - McGue, Matt A1 - David A Bennett A1 - Nancy L Pedersen A1 - Patrik K E Magnusson A1 - Ian J Deary A1 - Nicholas G Martin A1 - Dorret I Boomsma A1 - Bartels, Meike A1 - Luciano, Michelle KW - Genetics KW - Happiness KW - Polygenic Prediction KW - SSGAC KW - Well-being AB -

Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.

VL - 19 IS - 5 ER - TY - JOUR T1 - Directional dominance on stature and cognition in diverse human populations. JF - Nature Y1 - 2015 A1 - Joshi, Peter K A1 - Tõnu Esko A1 - Mattsson, Hannele A1 - Eklund, Niina A1 - Gandin, Ilaria A1 - Nutile, Teresa A1 - Jackson, Anne U A1 - Schurmann, Claudia A1 - Albert Vernon Smith A1 - Zhang, Weihua A1 - Okada, Yukinori A1 - Stančáková, Alena A1 - Jessica Faul A1 - Wei Zhao A1 - Traci M Bartz A1 - Maria Pina Concas A1 - Franceschini, Nora A1 - Enroth, Stefan A1 - Vitart, Veronique A1 - Trompet, Stella A1 - Guo, Xiuqing A1 - Daniel I Chasman A1 - Jeff O'Connell A1 - Corre, Tanguy A1 - Nongmaithem, Suraj S A1 - Chen, Yuning A1 - Mangino, Massimo A1 - Ruggiero, Daniela A1 - Traglia, Michela A1 - Farmaki, Aliki-Eleni A1 - Kacprowski, Tim A1 - Bjonnes, Andrew A1 - van der Spek, Ashley A1 - Wu, Ying A1 - Giri, Anil K A1 - Yanek, Lisa R A1 - Wang, Lihua A1 - Edith Hofer A1 - Cornelius A Rietveld A1 - McLeod, Olga A1 - Marilyn C Cornelis A1 - Pattaro, Cristian A1 - Verweij, Niek A1 - Baumbach, Clemens A1 - Abdel Abdellaoui A1 - Warren, Helen R A1 - Vuckovic, Dragana A1 - Mei, Hao A1 - Bouchard, Claude A1 - Perry, John R B A1 - Cappellani, Stefania A1 - Saira S Mirza A1 - Benton, Miles C A1 - Broeckel, Ulrich A1 - Sarah E Medland A1 - Penelope A Lind A1 - Malerba, Giovanni A1 - Alexander W Drong A1 - Yengo, Loic A1 - Bielak, Lawrence F A1 - Zhi, Degui A1 - van der Most, Peter J A1 - Daniel Shriner A1 - Mägi, Reedik A1 - Hemani, Gibran A1 - Karaderi, Tugce A1 - Wang, Zhaoming A1 - Tian Liu A1 - Demuth, Ilja A1 - Jing Hua Zhao A1 - Meng, Weihua A1 - Lataniotis, Lazaros A1 - van der Laan, Sander W A1 - Bradfield, Jonathan P A1 - Andrew R Wood A1 - Bonnefond, Amelie A1 - Ahluwalia, Tarunveer S A1 - Hall, Leanne M A1 - Salvi, Erika A1 - Yazar, Seyhan A1 - Carstensen, Lisbeth A1 - de Haan, Hugoline G A1 - Abney, Mark A1 - Afzal, Uzma A1 - Matthew A. Allison A1 - Amin, Najaf A1 - Asselbergs, Folkert W A1 - Bakker, Stephan J L A1 - Barr, R Graham A1 - Baumeister, Sebastian E A1 - Daniel J. Benjamin A1 - Bergmann, Sven A1 - Boerwinkle, Eric A1 - Erwin P Bottinger A1 - Campbell, Archie A1 - Chakravarti, Aravinda A1 - Chan, Yingleong A1 - Chanock, Stephen J A1 - Chen, Constance A1 - Yii-Der I Chen A1 - Collins, Francis S A1 - Connell, John A1 - Correa, Adolfo A1 - Cupples, L Adrienne A1 - Gail Davies A1 - Dörr, Marcus A1 - Georg B Ehret A1 - Ellis, Stephen B A1 - Feenstra, Bjarke A1 - Feitosa, Mary F A1 - Ford, Ian A1 - Caroline S Fox A1 - Timothy M Frayling A1 - Friedrich, Nele A1 - Geller, Frank A1 - Scotland, Generation A1 - Gillham-Nasenya, Irina A1 - Gottesman, Omri A1 - Graff, Misa A1 - Grodstein, Francine A1 - Gu, Charles A1 - Haley, Chris A1 - Hammond, Christopher J A1 - Sarah E Harris A1 - Tamara B Harris A1 - Nicholas D Hastie A1 - Heard-Costa, Nancy L A1 - Heikkilä, Kauko A1 - Lynne J Hocking A1 - Homuth, Georg A1 - Jouke-Jan Hottenga A1 - Huang, Jinyan A1 - Huffman, Jennifer E A1 - Hysi, Pirro G A1 - Mohammed Arfan Ikram A1 - Ingelsson, Erik A1 - Joensuu, Anni A1 - Johansson, Åsa A1 - Jousilahti, Pekka A1 - Jukema, J Wouter A1 - Kähönen, Mika A1 - Kamatani, Yoichiro A1 - Kanoni, Stavroula A1 - Kerr, Shona M A1 - Khan, Nazir M A1 - Philipp D Koellinger A1 - Koistinen, Heikki A A1 - Kooner, Manraj K A1 - Kubo, Michiaki A1 - Kuusisto, Johanna A1 - Lahti, Jari A1 - Lenore J Launer A1 - Lea, Rodney A A1 - Lehne, Benjamin A1 - Lehtimäki, Terho A1 - David C Liewald A1 - Lars Lind A1 - Loh, Marie A1 - Lokki, Marja-Liisa A1 - London, Stephanie J A1 - Loomis, Stephanie J A1 - Loukola, Anu A1 - Lu, Yingchang A1 - Lumley, Thomas A1 - Lundqvist, Annamari A1 - Männistö, Satu A1 - Marques-Vidal, Pedro A1 - Masciullo, Corrado A1 - Matchan, Angela A1 - Mathias, Rasika A A1 - Matsuda, Koichi A1 - Meigs, James B A1 - Meisinger, Christa A1 - Meitinger, Thomas A1 - Menni, Cristina A1 - Mentch, Frank D A1 - Mihailov, Evelin A1 - Lili Milani A1 - Montasser, May E A1 - Grant W Montgomery A1 - Alanna C Morrison A1 - Myers, Richard H A1 - Nadukuru, Rajiv A1 - Navarro, Pau A1 - Nelis, Mari A1 - Nieminen, Markku S A1 - Ilja M Nolte A1 - O'Connor, George T A1 - Ogunniyi, Adesola A1 - Padmanabhan, Sandosh A1 - Walter R Palmas A1 - Pankow, James S A1 - Patarcic, Inga A1 - Pavani, Francesca A1 - Peyser, Patricia A A1 - Pietilainen, Kirsi A1 - Neil Poulter A1 - Prokopenko, Inga A1 - Ralhan, Sarju A1 - Redmond, Paul A1 - Rich, Stephen S A1 - Rissanen, Harri A1 - Robino, Antonietta A1 - Rose, Lynda M A1 - Rose, Richard A1 - Cinzia Felicita Sala A1 - Babatunde Salako A1 - Veikko Salomaa A1 - Sarin, Antti-Pekka A1 - Saxena, Richa A1 - Schmidt, Helena A1 - Scott, Laura J A1 - Scott, William R A1 - Sennblad, Bengt A1 - Seshadri, Sudha A1 - Peter Sever A1 - Shrestha, Smeeta A1 - Smith, Blair H A1 - Jennifer A Smith A1 - Soranzo, Nicole A1 - Sotoodehnia, Nona A1 - Southam, Lorraine A1 - Stanton, Alice V A1 - Stathopoulou, Maria G A1 - Strauch, Konstantin A1 - Strawbridge, Rona J A1 - Suderman, Matthew J A1 - Tandon, Nikhil A1 - Tang, Sian-Tsun A1 - Kent D Taylor A1 - Bamidele O Tayo A1 - Töglhofer, Anna Maria A1 - Tomaszewski, Maciej A1 - Tšernikova, Natalia A1 - Tuomilehto, Jaakko A1 - André G Uitterlinden A1 - Vaidya, Dhananjay A1 - van Hylckama Vlieg, Astrid A1 - van Setten, Jessica A1 - Vasankari, Tuula A1 - Vedantam, Sailaja A1 - Vlachopoulou, Efthymia A1 - Vozzi, Diego A1 - Vuoksimaa, Eero A1 - Waldenberger, Melanie A1 - Erin B Ware A1 - Wentworth-Shields, William A1 - Whitfield, John B A1 - Sarah Wild A1 - Gonneke Willemsen A1 - Yajnik, Chittaranjan S A1 - Yao, Jie A1 - Zaza, Gianluigi A1 - Zhu, Xiaofeng A1 - Salem, Rany M A1 - Melbye, Mads A1 - Bisgaard, Hans A1 - Nilesh J Samani A1 - Cusi, Daniele A1 - Mackey, David A A1 - Cooper, Richard S A1 - Froguel, Philippe A1 - Pasterkamp, Gerard A1 - Grant, Struan F A A1 - Hakonarson, Hakon A1 - Luigi Ferrucci A1 - Scott, Robert A A1 - Morris, Andrew D A1 - Palmer, Colin N A A1 - George Dedoussis A1 - Deloukas, Panos A1 - Bertram, Lars A1 - Lindenberger, Ulman A1 - Berndt, Sonja I A1 - Lindgren, Cecilia M A1 - Nicholas J Timpson A1 - Tönjes, Anke A1 - Munroe, Patricia B A1 - Thorkild I. A. Sørensen A1 - Charles N Rotimi A1 - Donna K Arnett A1 - Oldehinkel, Albertine J A1 - Sharon L R Kardia A1 - Balkau, Beverley A1 - Gambaro, Giovanni A1 - Morris, Andrew P A1 - Johan G Eriksson A1 - Margaret J Wright A1 - Nicholas G Martin A1 - Hunt, Steven C A1 - John M Starr A1 - Ian J Deary A1 - Griffiths, Lyn R A1 - Henning Tiemeier A1 - Nicola Pirastu A1 - Kaprio, Jaakko A1 - Wareham, Nicholas J A1 - Pérusse, Louis A1 - Wilson, James G A1 - Giorgia G Girotto A1 - Caulfield, Mark J A1 - Olli T Raitakari A1 - Dorret I Boomsma A1 - Gieger, Christian A1 - van der Harst, Pim A1 - Hicks, Andrew A A1 - Kraft, Peter A1 - Sinisalo, Juha A1 - Knekt, Paul A1 - Johannesson, Magnus A1 - Patrik K E Magnusson A1 - Hamsten, Anders A1 - Schmidt, Reinhold A1 - Ingrid B Borecki A1 - Vartiainen, Erkki A1 - Becker, Diane M A1 - Bharadwaj, Dwaipayan A1 - Mohlke, Karen L A1 - Boehnke, Michael A1 - Cornelia M van Duijn A1 - Sanghera, Dharambir K A1 - Teumer, Alexander A1 - Zeggini, Eleftheria A1 - Andres Metspalu A1 - Paolo P. Gasparini A1 - Ulivi, Sheila A1 - Ober, Carole A1 - Toniolo, Daniela A1 - Rudan, Igor A1 - David J Porteous A1 - Ciullo, Marina A1 - Timothy Spector A1 - Caroline Hayward A1 - Dupuis, Josée A1 - Ruth J F Loos A1 - Alan F Wright A1 - Chandak, Giriraj R A1 - Vollenweider, Peter A1 - Alan R Shuldiner A1 - Ridker, Paul M A1 - Rotter, Jerome I A1 - Sattar, Naveed A1 - Gyllensten, Ulf A1 - Kari E North A1 - Pirastu, Mario A1 - Psaty, Bruce M A1 - David R Weir A1 - Laakso, Markku A1 - Gudnason, Vilmundur A1 - Takahashi, Atsushi A1 - Chambers, John C A1 - Kooner, Jaspal S A1 - David P Strachan A1 - Campbell, Harry A1 - Joel N Hirschhron A1 - Markus Perola A1 - Polasek, Ozren A1 - James F Wilson KW - Biological Evolution KW - Blood pressure KW - Body Height KW - Cholesterol KW - Cognitive Ability KW - Cohort Studies KW - Education KW - Female KW - Forced Expiratory Volume KW - Genome KW - Homozygote KW - Humans KW - Lung Volume Measurements KW - Male KW - Phenotype AB -

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

VL - 523 IS - 7561 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26131930?dopt=Abstract 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 -