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 - 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 - 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 - Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. JF - Nat Genet Y1 - 2018 A1 - Turcot, Valérie A1 - Lu, Yingchang A1 - Highland, Heather M A1 - Schurmann, Claudia A1 - Justice, Anne E A1 - Fine, Rebecca S A1 - Bradfield, Jonathan P A1 - Tõnu Esko A1 - Giri, Ayush A1 - Graff, Mariaelisa A1 - Guo, Xiuqing A1 - Hendricks, Audrey E A1 - Karaderi, Tugce A1 - Lempradl, Adelheid A1 - Locke, Adam E A1 - Mahajan, Anubha A1 - Marouli, Eirini A1 - Sivapalaratnam, Suthesh A1 - Young, Kristin L A1 - Alfred, Tamuno A1 - Feitosa, Mary F A1 - Masca, Nicholas G D A1 - Alisa Manning A1 - Medina-Gomez, Carolina A1 - Mudgal, Poorva A1 - Ng, Maggie C Y A1 - Reiner, Alex P A1 - Vedantam, Sailaja A1 - Willems, Sara M A1 - Thomas W Winkler A1 - Gonçalo R Abecasis A1 - Aben, Katja K A1 - Alam, Dewan S A1 - Alharthi, Sameer E A1 - Matthew A. Allison A1 - Amouyel, Philippe A1 - Asselbergs, Folkert W A1 - Auer, Paul L A1 - Balkau, Beverley A1 - Bang, Lia E A1 - Barroso, Inês A1 - Bastarache, Lisa A1 - Benn, Marianne A1 - Bergmann, Sven A1 - Bielak, Lawrence F A1 - Blüher, Matthias A1 - Boehnke, Michael A1 - Boeing, Heiner A1 - Boerwinkle, Eric A1 - Böger, Carsten A A1 - Bork-Jensen, Jette A1 - Bots, Michiel L A1 - Erwin P Bottinger A1 - Bowden, Donald W A1 - Brandslund, Ivan A1 - Breen, Gerome A1 - Brilliant, Murray H A1 - Broer, Linda A1 - Brumat, Marco A1 - Burt, Amber A A1 - Adam S Butterworth A1 - Campbell, Peter T A1 - Cappellani, Stefania A1 - Carey, David J A1 - Catamo, Eulalia A1 - Caulfield, Mark J A1 - Chambers, John C A1 - Daniel I Chasman A1 - Yii-Der I Chen A1 - Chowdhury, Rajiv A1 - Cramer Christensen A1 - Chu, Audrey Y A1 - Cocca, Massimiliano A1 - Collins, Francis S A1 - Cook, James P A1 - Corley, Janie A1 - Jordi Corominas Galbany A1 - Cox, Amanda J A1 - Crosslin, David S A1 - Cuellar-Partida, Gabriel A1 - D'Eustacchio, Angela A1 - Danesh, John A1 - Gail Davies A1 - Bakker, Paul I W A1 - Groot, Mark C H A1 - Mutsert, Renée A1 - Ian J Deary A1 - George Dedoussis A1 - Ellen W Demerath A1 - Heijer, Martin A1 - Anneke I den Hollander A1 - Hester M den Ruijter A1 - Joe G Dennis A1 - Denny, Josh C A1 - Angelantonio, Emanuele A1 - Drenos, Fotios A1 - Du, Mengmeng A1 - Dubé, Marie-Pierre A1 - Dunning, Alison M A1 - Easton, Douglas F A1 - Edwards, Todd L A1 - Ellinghaus, David A1 - Ellinor, Patrick T A1 - Elliott, Paul A1 - Evangelou, Evangelos A1 - Farmaki, Aliki-Eleni A1 - Farooqi, I Sadaf A1 - Jessica Faul A1 - Fauser, Sascha A1 - Feng, Shuang A1 - Ferrannini, Ele A1 - Ferrières, Jean A1 - Florez, Jose C A1 - Ford, Ian A1 - Myriam Fornage A1 - Franco, Oscar H A1 - Franke, Andre A1 - Franks, Paul W A1 - Friedrich, Nele A1 - Frikke-Schmidt, Ruth A1 - Galesloot, Tessel E A1 - Gan, Wei A1 - Gandin, Ilaria A1 - Paolo P. Gasparini A1 - Gibson, Jane A1 - Giedraitis, Vilmantas A1 - Gjesing, Anette P A1 - Gordon-Larsen, Penny A1 - Gorski, Mathias A1 - Hans-Jörgen Grabe A1 - Grant, Struan F A A1 - Grarup, Niels A1 - Griffiths, Helen L A1 - Grove, Megan L A1 - Gudnason, Vilmundur A1 - Gustafsson, Stefan A1 - Jeffrey Haessler A1 - Hakonarson, Hakon A1 - Anke R Hammerschlag A1 - Hansen, Torben A1 - Tamara B Harris A1 - Andrew T Hattersley A1 - Have, Christian T A1 - Caroline Hayward A1 - He, Liang A1 - Heard-Costa, Nancy L A1 - Andrew C Heath A1 - Iris M Heid A1 - Helgeland, Øyvind A1 - Hernesniemi, Jussi A1 - Hewitt, Alex W A1 - Oddgeir L Holmen A1 - Hovingh, G Kees A1 - Howson, Joanna M M A1 - Hu, Yao A1 - Huang, Paul L A1 - Huffman, Jennifer E A1 - Mohammed Arfan Ikram A1 - Ingelsson, Erik A1 - Jackson, Anne U A1 - Jansson, Jan-Håkan A1 - Jarvik, Gail P A1 - Jensen, Gorm B A1 - Jia, Yucheng A1 - Johansson, Stefan A1 - Jørgensen, Marit E A1 - Jørgensen, Torben A1 - Jukema, J Wouter A1 - Kahali, Bratati A1 - Kahn, René S A1 - Kähönen, Mika A1 - Kamstrup, Pia R A1 - Kanoni, Stavroula A1 - Kaprio, Jaakko A1 - Karaleftheri, Maria A1 - Sharon L R Kardia A1 - Karpe, Fredrik A1 - Kathiresan, Sekar A1 - Kee, Frank A1 - Lambertus A Kiemeney A1 - Eric S Kim A1 - Kitajima, Hidetoshi A1 - Komulainen, Pirjo A1 - Kooner, Jaspal S A1 - Charles Kooperberg A1 - Korhonen, Tellervo A1 - Kovacs, Peter A1 - Kuivaniemi, Helena A1 - Kutalik, Zoltán A1 - Kuulasmaa, Kari A1 - Kuusisto, Johanna A1 - Laakso, Markku A1 - Lakka, Timo A A1 - Lamparter, David A1 - Lange, Ethan M A1 - Leslie A Lange A1 - Langenberg, Claudia A1 - Eric B Larson A1 - Lee, Nanette R A1 - Lehtimäki, Terho A1 - Lewis, Cora E A1 - Li, Huaixing A1 - Li, Jin A1 - Li-Gao, Ruifang A1 - Lin, Honghuang A1 - Lin, Keng-Hung A1 - Lin, Li-An A1 - Lin, Xu A1 - Lars Lind A1 - Lindström, Jaana A1 - Linneberg, Allan A1 - Liu, Ching-Ti A1 - Liu, Dajiang J A1 - Yongmei Liu A1 - Ken Sin Lo A1 - Lophatananon, Artitaya A1 - Lotery, Andrew J A1 - Loukola, Anu A1 - Luan, Jian'an A1 - Lubitz, Steven A A1 - Lyytikäinen, Leo-Pekka A1 - Männistö, Satu A1 - Marenne, Gaëlle A1 - Mazul, Angela L A1 - McCarthy, Mark I A1 - McKean-Cowdin, Roberta A1 - Sarah E Medland A1 - Meidtner, Karina A1 - Lili Milani A1 - Mistry, Vanisha A1 - Mitchell, Paul A1 - Mohlke, Karen L A1 - Moilanen, Leena A1 - Moitry, Marie A1 - Grant W Montgomery A1 - Dennis O Mook-Kanamori A1 - Moore, Carmel A1 - Mori, Trevor A A1 - Morris, Andrew D A1 - Morris, Andrew P A1 - Müller-Nurasyid, Martina A1 - Munroe, Patricia B A1 - Michael A Nalls A1 - Narisu, Narisu A1 - Nelson, Christopher P A1 - Neville, Matt A1 - Sune Fallgaard Nielsen A1 - Nikus, Kjell A1 - Njølstad, Pål R A1 - Børge G Nordestgaard A1 - Nyholt, Dale R A1 - Jeff O'Connell A1 - O'Donoghue, Michelle L A1 - Ophoff, Roel A A1 - Owen, Katharine R A1 - Packard, Chris J A1 - Padmanabhan, Sandosh A1 - Palmer, Colin N A A1 - Palmer, Nicholette D A1 - Pasterkamp, Gerard A1 - Patel, Aniruddh P A1 - Pattie, Alison A1 - Pedersen, Oluf A1 - Peissig, Peggy L A1 - Peloso, Gina M A1 - Pennell, Craig E A1 - Markus Perola A1 - Perry, James A A1 - Perry, John R B A1 - Pers, Tune H A1 - Person, Thomas N A1 - Peters, Annette A1 - Petersen, Eva R B A1 - Peyser, Patricia A A1 - Pirie, Ailith A1 - Polasek, Ozren A1 - Tinca J Polderman A1 - Puolijoki, Hannu A1 - Olli T Raitakari A1 - Rasheed, Asif A1 - Rauramaa, Rainer A1 - Reilly, Dermot F A1 - Renstrom, Frida A1 - Rheinberger, Myriam A1 - Ridker, Paul M A1 - Rioux, John D A1 - Rivas, Manuel A A1 - Roberts, David J A1 - Neil R Robertson A1 - Robino, Antonietta A1 - Rolandsson, Olov A1 - Rudan, Igor A1 - Ruth, Katherine S A1 - Saleheen, Danish A1 - Veikko Salomaa A1 - Nilesh J Samani A1 - Sapkota, Yadav A1 - Sattar, Naveed A1 - Schoen, Robert E A1 - Schreiner, Pamela J A1 - Schulze, Matthias B A1 - Scott, Robert A A1 - Segura-Lepe, Marcelo P A1 - Svati H Shah A1 - Sheu, Wayne H-H A1 - Sim, Xueling A1 - Slater, Andrew J A1 - Small, Kerrin S A1 - Albert Vernon Smith A1 - Southam, Lorraine A1 - Timothy Spector A1 - Elizabeth K Speliotes A1 - John M Starr A1 - Stefansson, Kari A1 - Steinthorsdottir, Valgerdur A1 - Kathleen E Stirrups A1 - Strauch, Konstantin A1 - Heather M Stringham A1 - Stumvoll, Michael A1 - Sun, Liang A1 - Surendran, Praveen A1 - Swift, Amy J A1 - Tada, Hayato A1 - Tansey, Katherine E A1 - Tardif, Jean-Claude A1 - Kent D Taylor A1 - Teumer, Alexander A1 - Thompson, Deborah J A1 - Thorleifsson, Gudmar A1 - Thorsteinsdottir, Unnur A1 - Thuesen, Betina H A1 - Tönjes, Anke A1 - Tromp, Gerard A1 - Trompet, Stella A1 - Tsafantakis, Emmanouil A1 - Tuomilehto, Jaakko A1 - Tybjaerg-Hansen, Anne A1 - Tyrer, Jonathan P A1 - Uher, Rudolf A1 - André G Uitterlinden A1 - Uusitupa, Matti A1 - Laan, Sander W A1 - Duijn, Cornelia M A1 - Leeuwen, Nienke A1 - van Setten, Jessica A1 - Vanhala, Mauno A1 - Varbo, Anette A1 - Varga, Tibor V A1 - Varma, Rohit A1 - Digna R Velez Edwards A1 - Vermeulen, Sita H A1 - Veronesi, Giovanni A1 - Vestergaard, Henrik A1 - Vitart, Veronique A1 - Vogt, Thomas F A1 - Völker, Uwe A1 - Vuckovic, Dragana A1 - Wagenknecht, Lynne E A1 - Walker, Mark A1 - Wallentin, Lars A1 - Wang, Feijie A1 - Wang, Carol A A1 - Wang, Shuai A1 - Wang, Yiqin A1 - Erin B Ware A1 - Wareham, Nicholas J A1 - Warren, Helen R A1 - Dawn M Waterworth A1 - Wessel, Jennifer A1 - White, Harvey D A1 - Willer, Cristen J A1 - Wilson, James G A1 - Daniel Witte A1 - Andrew R Wood A1 - Wu, Ying A1 - Yaghootkar, Hanieh A1 - Yao, Jie A1 - Yao, Pang A1 - Laura M Yerges-Armstrong A1 - Young, Robin A1 - Zeggini, Eleftheria A1 - Zhan, Xiaowei A1 - Zhang, Weihua A1 - Wei Zhao A1 - Zhou, Wei A1 - Krina T Zondervan A1 - Rotter, Jerome I A1 - Pospisilik, John A A1 - Fernando Rivadeneira A1 - Ingrid B Borecki A1 - Deloukas, Panos A1 - Timothy M Frayling A1 - Lettre, Guillaume A1 - Kari E North A1 - Lindgren, Cecilia M A1 - Joel N Hirschhron A1 - Ruth J F Loos AB -

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

VL - 50 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/29273807?dopt=Abstract ER - TY - JOUR T1 - Rare and low-frequency coding variants alter human adult height. JF - Nature Y1 - 2017 A1 - Marouli, Eirini A1 - Graff, Mariaelisa A1 - Medina-Gomez, Carolina A1 - Ken Sin Lo A1 - Andrew R Wood A1 - Kjaer, Troels R A1 - Fine, Rebecca S A1 - Lu, Yingchang A1 - Schurmann, Claudia A1 - Highland, Heather M A1 - Rüeger, Sina A1 - Thorleifsson, Gudmar A1 - Justice, Anne E A1 - Lamparter, David A1 - Kathleen E Stirrups A1 - Turcot, Valérie A1 - Young, Kristin L A1 - Thomas W Winkler A1 - Tõnu Esko A1 - Karaderi, Tugce A1 - Locke, Adam E A1 - Masca, Nicholas G D A1 - Ng, Maggie C Y A1 - Mudgal, Poorva A1 - Rivas, Manuel A A1 - Vedantam, Sailaja A1 - Mahajan, Anubha A1 - Guo, Xiuqing A1 - Gonçalo R Abecasis A1 - Aben, Katja K A1 - Adair, Linda S A1 - Alam, Dewan S A1 - Albrecht, Eva A1 - Allin, Kristine H A1 - Matthew A. Allison A1 - Amouyel, Philippe A1 - Appel, Emil V A1 - Arveiler, Dominique A1 - Asselbergs, Folkert W A1 - Auer, Paul L A1 - Balkau, Beverley A1 - Banas, Bernhard A1 - Bang, Lia E A1 - Benn, Marianne A1 - Bergmann, Sven A1 - Bielak, Lawrence F A1 - Blüher, Matthias A1 - Boeing, Heiner A1 - Boerwinkle, Eric A1 - Böger, Carsten A A1 - Bonnycastle, Lori L A1 - Bork-Jensen, Jette A1 - Bots, Michiel L A1 - Erwin P Bottinger A1 - Bowden, Donald W A1 - Brandslund, Ivan A1 - Breen, Gerome A1 - Brilliant, Murray H A1 - Broer, Linda A1 - Burt, Amber A A1 - Adam S Butterworth A1 - Carey, David J A1 - Caulfield, Mark J A1 - Chambers, John C A1 - Daniel I Chasman A1 - Yii-Der I Chen A1 - Chowdhury, Rajiv A1 - Cramer Christensen A1 - Chu, Audrey Y A1 - Cocca, Massimiliano A1 - Collins, Francis S A1 - Cook, James P A1 - Corley, Janie A1 - Jordi Corominas Galbany A1 - Cox, Amanda J A1 - Cuellar-Partida, Gabriel A1 - Danesh, John A1 - Gail Davies A1 - de Bakker, Paul I W A1 - de Borst, Gert J A1 - de Denus, Simon A1 - de Groot, Mark C H A1 - de Mutsert, Renée A1 - Ian J Deary A1 - George Dedoussis A1 - Ellen W Demerath A1 - Anneke I den Hollander A1 - Joe G Dennis A1 - Di Angelantonio, Emanuele A1 - Drenos, Fotios A1 - Du, Mengmeng A1 - Dunning, Alison M A1 - Easton, Douglas F A1 - Ebeling, Tapani A1 - Edwards, Todd L A1 - Ellinor, Patrick T A1 - Elliott, Paul A1 - Evangelou, Evangelos A1 - Farmaki, Aliki-Eleni A1 - Jessica Faul A1 - Feitosa, Mary F A1 - Feng, Shuang A1 - Ferrannini, Ele A1 - Marco M Ferrario A1 - Ferrières, Jean A1 - Florez, Jose C A1 - Ford, Ian A1 - Myriam Fornage A1 - Franks, Paul W A1 - Frikke-Schmidt, Ruth A1 - Galesloot, Tessel E A1 - Gan, Wei A1 - Gandin, Ilaria A1 - Paolo P. Gasparini A1 - Giedraitis, Vilmantas A1 - Giri, Ayush A1 - Giorgia G Girotto A1 - Gordon, Scott D A1 - Gordon-Larsen, Penny A1 - Gorski, Mathias A1 - Grarup, Niels A1 - Grove, Megan L A1 - Gudnason, Vilmundur A1 - Gustafsson, Stefan A1 - Hansen, Torben A1 - Kathleen Mullan Harris A1 - Tamara B Harris A1 - Andrew T Hattersley A1 - Caroline Hayward A1 - He, Liang A1 - Iris M Heid A1 - Heikkilä, Kauko A1 - Helgeland, Øyvind A1 - Hernesniemi, Jussi A1 - Hewitt, Alex W A1 - Lynne J Hocking A1 - Hollensted, Mette A1 - Oddgeir L Holmen A1 - Hovingh, G Kees A1 - Howson, Joanna M M A1 - Hoyng, Carel B A1 - Huang, Paul L A1 - Hveem, Kristian A1 - Mohammed Arfan Ikram A1 - Ingelsson, Erik A1 - Jackson, Anne U A1 - Jansson, Jan-Håkan A1 - Jarvik, Gail P A1 - Jensen, Gorm B A1 - Jhun, Min A A1 - Jia, Yucheng A1 - Jiang, Xuejuan A1 - Johansson, Stefan A1 - Jørgensen, Marit E A1 - Jørgensen, Torben A1 - Jousilahti, Pekka A1 - Jukema, J Wouter A1 - Kahali, Bratati A1 - Kahn, René S A1 - Kähönen, Mika A1 - Kamstrup, Pia R A1 - Kanoni, Stavroula A1 - Kaprio, Jaakko A1 - Karaleftheri, Maria A1 - Sharon L R Kardia A1 - Karpe, Fredrik A1 - Kee, Frank A1 - Keeman, Renske A1 - Lambertus A Kiemeney A1 - Kitajima, Hidetoshi A1 - Kluivers, Kirsten B A1 - Kocher, Thomas A1 - Komulainen, Pirjo A1 - Kontto, Jukka A1 - Kooner, Jaspal S A1 - Charles Kooperberg A1 - Kovacs, Peter A1 - Kriebel, Jennifer A1 - Kuivaniemi, Helena A1 - Küry, Sébastien A1 - Kuusisto, Johanna A1 - La Bianca, Martina A1 - Laakso, Markku A1 - Lakka, Timo A A1 - Lange, Ethan M A1 - Leslie A Lange A1 - Langefeld, Carl D A1 - Langenberg, Claudia A1 - Eric B Larson A1 - Lee, I-Te A1 - Lehtimäki, Terho A1 - Lewis, Cora E A1 - Li, Huaixing A1 - Li, Jin A1 - Li-Gao, Ruifang A1 - Lin, Honghuang A1 - Lin, Li-An A1 - Lin, Xu A1 - Lars Lind A1 - Lindström, Jaana A1 - Linneberg, Allan A1 - Liu, Yeheng A1 - Yongmei Liu A1 - Lophatananon, Artitaya A1 - Luan, Jian'an A1 - Lubitz, Steven A A1 - Lyytikäinen, Leo-Pekka A1 - Mackey, David A A1 - Pamela A F Madden A1 - Alisa Manning A1 - Männistö, Satu A1 - Marenne, Gaëlle A1 - Marten, Jonathan A1 - Nicholas G Martin A1 - Mazul, Angela L A1 - Meidtner, Karina A1 - Andres Metspalu A1 - Mitchell, Paul A1 - Mohlke, Karen L A1 - Dennis O Mook-Kanamori A1 - Morgan, Anna A1 - Morris, Andrew D A1 - Morris, Andrew P A1 - Müller-Nurasyid, Martina A1 - Munroe, Patricia B A1 - Michael A Nalls A1 - Nauck, Matthias A1 - Nelson, Christopher P A1 - Neville, Matt A1 - Sune Fallgaard Nielsen A1 - Nikus, Kjell A1 - Njølstad, Pål R A1 - Børge G Nordestgaard A1 - Ntalla, Ioanna A1 - Jeff O'Connell A1 - Oksa, Heikki A1 - Loes M Olde Loohuis A1 - Ophoff, Roel A A1 - Owen, Katharine R A1 - Packard, Chris J A1 - Padmanabhan, Sandosh A1 - Palmer, Colin N A A1 - Pasterkamp, Gerard A1 - Patel, Aniruddh P A1 - Pattie, Alison A1 - Pedersen, Oluf A1 - Peissig, Peggy L A1 - Peloso, Gina M A1 - Pennell, Craig E A1 - Markus Perola A1 - Perry, James A A1 - Perry, John R B A1 - Person, Thomas N A1 - Pirie, Ailith A1 - Polasek, Ozren A1 - Posthuma, Danielle A1 - Olli T Raitakari A1 - Rasheed, Asif A1 - Rauramaa, Rainer A1 - Reilly, Dermot F A1 - Reiner, Alex P A1 - Renstrom, Frida A1 - Ridker, Paul M A1 - Rioux, John D A1 - Neil R Robertson A1 - Robino, Antonietta A1 - Rolandsson, Olov A1 - Rudan, Igor A1 - Ruth, Katherine S A1 - Saleheen, Danish A1 - Veikko Salomaa A1 - Nilesh J Samani A1 - Sandow, Kevin A1 - Sapkota, Yadav A1 - Sattar, Naveed A1 - Schmidt, Marjanka K A1 - Schreiner, Pamela J A1 - Schulze, Matthias B A1 - Scott, Robert A A1 - Segura-Lepe, Marcelo P A1 - Svati H Shah A1 - Sim, Xueling A1 - Sivapalaratnam, Suthesh A1 - Small, Kerrin S A1 - Albert Vernon Smith A1 - Jennifer A Smith A1 - Southam, Lorraine A1 - Timothy Spector A1 - Elizabeth K Speliotes A1 - John M Starr A1 - Steinthorsdottir, Valgerdur A1 - Heather M Stringham A1 - Stumvoll, Michael A1 - Surendran, Praveen A1 - 't Hart, Leen M A1 - Tansey, Katherine E A1 - Tardif, Jean-Claude A1 - Kent D Taylor A1 - Teumer, Alexander A1 - Thompson, Deborah J A1 - Thorsteinsdottir, Unnur A1 - Thuesen, Betina H A1 - Tönjes, Anke A1 - Tromp, Gerard A1 - Trompet, Stella A1 - Tsafantakis, Emmanouil A1 - Tuomilehto, Jaakko A1 - Tybjaerg-Hansen, Anne A1 - Tyrer, Jonathan P A1 - Uher, Rudolf A1 - André G Uitterlinden A1 - Ulivi, Sheila A1 - van der Laan, Sander W A1 - Van Der Leij, Andries R A1 - Cornelia M van Duijn A1 - van Schoor, Natasja M A1 - van Setten, Jessica A1 - Varbo, Anette A1 - Varga, Tibor V A1 - Varma, Rohit A1 - Digna R Velez Edwards A1 - Vermeulen, Sita H A1 - Vestergaard, Henrik A1 - Vitart, Veronique A1 - Vogt, Thomas F A1 - Vozzi, Diego A1 - Walker, Mark A1 - Wang, Feijie A1 - Wang, Carol A A1 - Wang, Shuai A1 - Wang, Yiqin A1 - Wareham, Nicholas J A1 - Warren, Helen R A1 - Wessel, Jennifer A1 - Willems, Sara M A1 - Wilson, James G A1 - Daniel Witte A1 - Woods, Michael O A1 - Wu, Ying A1 - Yaghootkar, Hanieh A1 - Yao, Jie A1 - Yao, Pang A1 - Laura M Yerges-Armstrong A1 - Young, Robin A1 - Zeggini, Eleftheria A1 - Zhan, Xiaowei A1 - Zhang, Weihua A1 - Jing Hua Zhao A1 - Wei Zhao A1 - Wei Zhao A1 - Zheng, He A1 - Zhou, Wei A1 - Rotter, Jerome I A1 - Boehnke, Michael A1 - Kathiresan, Sekar A1 - McCarthy, Mark I A1 - Willer, Cristen J A1 - Stefansson, Kari A1 - Ingrid B Borecki A1 - Liu, Dajiang J A1 - Kari E North A1 - Heard-Costa, Nancy L A1 - Pers, Tune H A1 - Lindgren, Cecilia M A1 - Oxvig, Claus A1 - Kutalik, Zoltán A1 - Fernando Rivadeneira A1 - Ruth J F Loos A1 - Timothy M Frayling A1 - Joel N Hirschhron A1 - Deloukas, Panos A1 - Lettre, Guillaume AB -

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

VL - 542 IS - 7640 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28146470?dopt=Abstract ER - TY - JOUR T1 - SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function. JF - Journal of the American Society of Nephrology Y1 - 2017 A1 - Li, Man A1 - Li, Yong A1 - Weeks, Olivia A1 - Mijatovic, Vladan A1 - Teumer, Alexander A1 - Huffman, Jennifer E A1 - Tromp, Gerard A1 - Fuchsberger, Christian A1 - Gorski, Mathias A1 - Lyytikäinen, Leo-Pekka A1 - Nutile, Teresa A1 - Sedaghat, Sanaz A1 - Sorice, Rossella A1 - Tin, Adrienne A1 - Yang, Qiong A1 - Ahluwalia, Tarunveer S A1 - Dan E Arking A1 - Bihlmeyer, Nathan A A1 - Böger, Carsten A A1 - Carroll, Robert J A1 - Daniel I Chasman A1 - Marilyn C Cornelis A1 - Dehghan, Abbas A1 - Jessica Faul A1 - Feitosa, Mary F A1 - Gambaro, Giovanni A1 - Paolo P. Gasparini A1 - Giulianini, Franco A1 - Iris M Heid A1 - Huang, Jinyan A1 - Imboden, Medea A1 - Jackson, Anne U A1 - Janina Jeff A1 - Jhun, Min A A1 - Katz, Ronit A1 - Kifley, Annette A1 - Kilpeläinen, Tuomas O A1 - Kumar, Ashish A1 - Laakso, Markku A1 - Li-Gao, Ruifang A1 - Kurt Lohman A1 - Lu, Yingchang A1 - Mägi, Reedik A1 - Malerba, Giovanni A1 - Mihailov, Evelin A1 - Mohlke, Karen L A1 - Dennis O Mook-Kanamori A1 - Robino, Antonietta A1 - Ruderfer, Douglas A1 - Salvi, Erika A1 - Schick, Ursula M A1 - Schulz, Christina-Alexandra A1 - Smith, Albert V A1 - Smith, Jennifer A A1 - Traglia, Michela A1 - Laura M Yerges-Armstrong A1 - Zhao, Wei A1 - Goodarzi, Mark O A1 - Kraja, Aldi T A1 - Liu, Chunyu A1 - Wessel, Jennifer A1 - Boerwinkle, Eric A1 - Ingrid B Borecki A1 - Bork-Jensen, Jette A1 - Erwin P Bottinger A1 - Braga, Daniele A1 - Brandslund, Ivan A1 - Brody, Jennifer A A1 - Campbell, Archie A1 - Carey, David J A1 - Cramer Christensen A1 - Coresh, Josef A1 - Crook, Errol A1 - Curhan, Gary C A1 - Cusi, Daniele A1 - de Boer, Ian H A1 - de Vries, Aiko P J A1 - Denny, Joshua C A1 - Devuyst, Olivier A1 - Dreisbach, Albert W A1 - Endlich, Karlhans A1 - Tõnu Esko A1 - Franco, Oscar H A1 - Fulop, Tibor A1 - Gerhard, Glenn S A1 - Glümer, Charlotte A1 - Gottesman, Omri A1 - Grarup, Niels A1 - Gudnason, Vilmundur A1 - Hansen, Torben A1 - Tamara B Harris A1 - Caroline Hayward A1 - Lynne J Hocking A1 - Hofman, Albert A1 - Hu, Frank B A1 - Husemoen, Lise Lotte N A1 - Jackson, Rebecca D A1 - Jørgensen, Torben A1 - Jørgensen, Marit E A1 - Kähönen, Mika A1 - Sharon L R Kardia A1 - König, Wolfgang A1 - Charles Kooperberg A1 - Kriebel, Jennifer A1 - Lenore J Launer A1 - Lauritzen, Torsten A1 - Lehtimäki, Terho A1 - Levy, Daniel A1 - Linksted, Pamela A1 - Linneberg, Allan A1 - Liu, Yongmei A1 - Ruth J F Loos A1 - Lupo, Antonio A1 - Meisinger, Christine A1 - Melander, Olle A1 - Andres Metspalu A1 - Mitchell, Paul A1 - Nauck, Matthias A1 - Nürnberg, Peter A1 - Orho-Melander, Marju A1 - Parsa, Afshin A1 - Pedersen, Oluf A1 - Peters, Annette A1 - Peters, Ulrike A1 - Polasek, Ozren A1 - David J Porteous A1 - Nicole M Probst-Hensch A1 - Psaty, Bruce M A1 - Qi, Lu A1 - Olli T Raitakari A1 - Reiner, Alex P A1 - Rettig, Rainer A1 - Ridker, Paul M A1 - Fernando Rivadeneira A1 - Rossouw, Jacques E A1 - Schmidt, Frank A1 - David S Siscovick A1 - Soranzo, Nicole A1 - Strauch, Konstantin A1 - Toniolo, Daniela A1 - Stephen T Turner A1 - André G Uitterlinden A1 - Ulivi, Sheila A1 - Velayutham, Dinesh A1 - Völker, Uwe A1 - Völzke, Henry A1 - Waldenberger, Melanie A1 - Wang, Jie Jin A1 - David R Weir A1 - Daniel Witte A1 - Kuivaniemi, Helena A1 - Caroline S Fox A1 - Franceschini, Nora A1 - Goessling, Wolfram A1 - Köttgen, Anna A1 - Chu, Audrey Y KW - Animals KW - Exome KW - Genetic Loci KW - Genome-Wide Association Study KW - Glomerular Filtration Rate KW - Humans KW - kidney KW - Protein Tyrosine Phosphatases KW - Proto-Oncogene Proteins KW - Son of Sevenless Proteins KW - Zebrafish AB -

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

VL - 28 IS - 3 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 - 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 - 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 - TY - JOUR T1 - Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair. JF - Nat Genet Y1 - 2015 A1 - Day, Felix R A1 - Ruth, Katherine S A1 - Thompson, Deborah J A1 - Kathryn L Lunetta A1 - Pervjakova, Natalia A1 - Daniel I Chasman A1 - Stolk, Lisette A1 - Finucane, Hilary K A1 - Sulem, Patrick A1 - Bulik-Sullivan, Brendan A1 - Tõnu Esko A1 - Andrew D Johnson A1 - Elks, Cathy E A1 - Franceschini, Nora A1 - He, Chunyan A1 - Altmaier, Elisabeth A1 - Brody, Jennifer A A1 - Lude L Franke A1 - Huffman, Jennifer E A1 - Keller, Margaux F A1 - McArdle, Patrick F A1 - Nutile, Teresa A1 - Porcu, Eleonora A1 - Robino, Antonietta A1 - Rose, Lynda M A1 - Schick, Ursula M A1 - Jennifer A Smith A1 - Teumer, Alexander A1 - Traglia, Michela A1 - Vuckovic, Dragana A1 - Yao, Jie A1 - Wei Zhao A1 - Albrecht, Eva A1 - Amin, Najaf A1 - Corre, Tanguy A1 - Jouke-Jan Hottenga A1 - Mangino, Massimo A1 - Albert Vernon Smith A1 - Toshiko Tanaka A1 - Gonçalo R Abecasis A1 - Andrulis, Irene L A1 - Anton-Culver, Hoda A1 - Antoniou, Antonis C A1 - Arndt, Volker A1 - Alice M. Arnold A1 - Barbieri, Caterina A1 - Beckmann, Matthias W A1 - Beeghly-Fadiel, Alicia A1 - Benitez, Javier A1 - Bernstein, Leslie A1 - Bielinski, Suzette J A1 - Blomqvist, Carl A1 - Boerwinkle, Eric A1 - Bogdanova, Natalia V A1 - Bojesen, Stig E A1 - Manjeet K. Bolla A1 - Borresen-Dale, Anne-Lise A1 - Boutin, Thibaud S A1 - Brauch, Hiltrud A1 - Brenner, Hermann A1 - Brüning, Thomas A1 - Burwinkel, Barbara A1 - Campbell, Archie A1 - Campbell, Harry A1 - Chanock, Stephen J A1 - Chapman, J Ross A1 - Yii-Der I Chen A1 - Chenevix-Trench, Georgia A1 - Couch, Fergus J A1 - Coviello, Andrea D A1 - Cox, Angela A1 - Czene, Kamila A1 - Darabi, Hatef A1 - De Vivo, Immaculata A1 - Ellen W Demerath A1 - Joe G Dennis A1 - Devilee, Peter A1 - Dörk, Thilo A1 - Dos-Santos-Silva, Isabel A1 - Dunning, Alison M A1 - John D Eicher A1 - Fasching, Peter A A1 - Jessica Faul A1 - Figueroa, Jonine A1 - Flesch-Janys, Dieter A1 - Gandin, Ilaria A1 - Melissa E Garcia A1 - García-Closas, Montserrat A1 - Giles, Graham G A1 - Giorgia G Girotto A1 - Goldberg, Mark S A1 - González-Neira, Anna A1 - Goodarzi, Mark O A1 - Grove, Megan L A1 - Gudbjartsson, Daniel F A1 - Guénel, Pascal A1 - Guo, Xiuqing A1 - Christopher A Haiman A1 - Hall, Per A1 - Hamann, Ute A1 - Henderson, Brian E A1 - Lynne J Hocking A1 - Hofman, Albert A1 - Homuth, Georg A1 - Hooning, Maartje J A1 - John L Hopper A1 - Hu, Frank B A1 - Huang, Jinyan A1 - Humphreys, Keith A1 - Hunter, David J A1 - Jakubowska, Anna A1 - Jones, Samuel E A1 - Kabisch, Maria A1 - Karasik, David A1 - Knight, Julia A A1 - Kolcic, Ivana A1 - Charles Kooperberg A1 - Kosma, Veli-Matti A1 - Kriebel, Jennifer A1 - Kristensen, Vessela A1 - Lambrechts, Diether A1 - Langenberg, Claudia A1 - Li, Jingmei A1 - Li, Xin A1 - Lindström, Sara A1 - Yongmei Liu A1 - Luan, Jian'an A1 - Lubinski, Jan A1 - Mägi, Reedik A1 - Mannermaa, Arto A1 - Manz, Judith A1 - Margolin, Sara A1 - Marten, Jonathan A1 - Nicholas G Martin A1 - Masciullo, Corrado A1 - Meindl, Alfons A1 - Michailidou, Kyriaki A1 - Mihailov, Evelin A1 - Lili Milani A1 - Milne, Roger L A1 - Müller-Nurasyid, Martina A1 - Michael A Nalls A1 - Neale, Benjamin M A1 - Nevanlinna, Heli A1 - Neven, Patrick A1 - Anne B Newman A1 - Børge G Nordestgaard A1 - Olson, Janet E A1 - Padmanabhan, Sandosh A1 - Peterlongo, Paolo A1 - Peters, Ulrike A1 - Petersmann, Astrid A1 - Peto, Julian A1 - Pharoah, Paul D P A1 - Nicola Pirastu A1 - Pirie, Ailith A1 - Pistis, Giorgio A1 - Polasek, Ozren A1 - David J Porteous A1 - Psaty, Bruce M A1 - Pylkäs, Katri A1 - Radice, Paolo A1 - Raffel, Leslie J A1 - Fernando Rivadeneira A1 - Rudan, Igor A1 - Rudolph, Anja A1 - Ruggiero, Daniela A1 - Cinzia Felicita Sala A1 - Sanna, Serena A1 - Sawyer, Elinor J A1 - Schlessinger, David A1 - Schmidt, Marjanka K A1 - Schmidt, Frank A1 - Schmutzler, Rita K A1 - Schoemaker, Minouk J A1 - Scott, Robert A A1 - Seynaeve, Caroline M A1 - Simard, Jacques A1 - Sorice, Rossella A1 - Southey, Melissa C A1 - Stöckl, Doris A1 - Strauch, Konstantin A1 - Swerdlow, Anthony A1 - Kent D Taylor A1 - Thorsteinsdottir, Unnur A1 - Toland, Amanda E A1 - Tomlinson, Ian A1 - Truong, Thérèse A1 - Tryggvadottir, Laufey A1 - Stephen T Turner A1 - Vozzi, Diego A1 - Wang, Qin A1 - Wellons, Melissa A1 - Gonneke Willemsen A1 - James F Wilson A1 - Winqvist, Robert A1 - Wolffenbuttel, Bruce B H R A1 - Alan F Wright A1 - Yannoukakos, Drakoulis A1 - Zemunik, Tatijana A1 - Wei Zhang A1 - Zygmunt, Marek A1 - Bergmann, Sven A1 - Dorret I Boomsma A1 - Buring, Julie E A1 - Luigi Ferrucci A1 - Grant W Montgomery A1 - Gudnason, Vilmundur A1 - Timothy Spector A1 - Cornelia M van Duijn A1 - Alizadeh, Behrooz Z A1 - Ciullo, Marina A1 - Crisponi, Laura A1 - Easton, Douglas F A1 - Paolo P. Gasparini A1 - Gieger, Christian A1 - Tamara B Harris A1 - Caroline Hayward A1 - Sharon L R Kardia A1 - Kraft, Peter A1 - McKnight, Barbara A1 - Andres Metspalu A1 - Alanna C Morrison A1 - Reiner, Alex P A1 - Ridker, Paul M A1 - Rotter, Jerome I A1 - Toniolo, Daniela A1 - André G Uitterlinden A1 - Ulivi, Sheila A1 - Völzke, Henry A1 - Wareham, Nicholas J A1 - David R Weir A1 - Laura M Yerges-Armstrong A1 - Price, Alkes L A1 - Stefansson, Kari A1 - Visser, Jenny A A1 - Ong, Ken K A1 - Chang-Claude, Jenny A1 - Joanne M Murabito A1 - Perry, John R B A1 - Murray, Anna KW - Age Factors KW - Aging KW - BRCA1 Protein KW - Breast Neoplasms KW - DNA Repair KW - Female KW - Genome KW - Genome-Wide Association Study KW - Genotype KW - Humans KW - Hypothalamus KW - Menopause KW - Middle Aged KW - Models, Genetic KW - Older Adults KW - Phenotype KW - Reproduction KW - Signal Transduction AB -

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

VL - 47 IS - 11 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26414677?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 -