%0 Journal Article %J Nature Genetics %D 2018 %T Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence %A Savage, Jeanne E. %A Philip R Jansen %A Stringer, Sven %A Watanabe, Kyoko %A Bryois, Julien %A Christiaan de Leeuw %A Nagel, Mats %A Awasthi, Swapnil %A Barr, Peter B. %A Coleman, Jonathan R. I. %A Grasby, Katrina L. %A Anke R Hammerschlag %A Kaminski, Jakob A. %A Karlsson, Robert %A Krapohl, Eva %A Lam, Max %A Nygaard, Marianne %A Chandra A Reynolds %A Joey W Trampush %A Young, Hannah %A Zabaneh, Delilah %A Hägg, Sara %A Narelle K Hansell %A Ida Karlsson %A Linnarsson, Sten %A Grant W Montgomery %A Muñoz-Manchado, Ana B. %A Quinlan, Erin B. %A Schumann, Gunter %A Skene, Nathan G. %A Webb, Bradley T. %A White, Tonya %A Dan E Arking %A Avramopoulos, Dimitrios %A Robert M Bilder %A Bitsios, Panos %A Katherine E Burdick %A Tyrone D. Cannon %A Chiba-Falek, Ornit %A Christoforou, Andrea %A Elizabeth T. Cirulli %A Congdon, Eliza %A Corvin, Aiden %A Gail Davies %A Ian J Deary %A DeRosse, Pamela %A Dickinson, Dwight %A Djurovic, Srdjan %A Donohoe, Gary %A Conley, Emily Drabant %A Johan G Eriksson %A Espeseth, Thomas %A Nelson A. Freimer %A Giakoumaki, Stella %A Giegling, Ina %A Gill, Michael %A David C. Glahn %A Ahmad R Hariri %A Hatzimanolis, Alex %A Matthew C Keller %A Knowles, Emma %A Koltai, Deborah %A Konte, Bettina %A Lahti, Jari %A Stephanie Le Hellard %A Lencz, Todd %A David C Liewald %A London, Edythe %A Astri J Lundervold %A Anil K. Malhotra %A Melle, Ingrid %A Morris, Derek %A Anna C Need %A William E R Ollier %A Aarno Palotie %A Payton, Antony %A Pendleton, Neil %A Russell A Poldrack %A Katri Räikkönen %A Reinvang, Ivar %A Roussos, Panos %A Rujescu, Dan %A Fred W Sabb %A Matthew A Scult %A Smeland, Olav B. %A Smyrnis, Nikolaos %A John M Starr %A Vidar M Steen %A Nikos C Stefanis %A Richard E Straub %A Sundet, Kjetil %A Henning Tiemeier %A Aristotle N Voineskos %A Daniel R Weinberger %A Elisabeth Widen %A Yu, Jin %A Gonçalo R Abecasis %A Andreassen, Ole A. %A Breen, Gerome %A Christiansen, Lene %A Debrabant, Birgit %A Danielle M. Dick %A Heinz, Andreas %A Hjerling-Leffler, Jens %A Mohammed Arfan Ikram %A Kendler, Kenneth S. %A Nicholas G Martin %A Sarah E Medland %A Nancy L Pedersen %A Plomin, Robert %A Tinca J Polderman %A Ripke, Stephan %A van der Sluis, Sophie %A Patrick F. Sullivan %A Scott Vrieze %A Margaret J Wright %A Posthuma, Danielle %K Genome-Wide Association Study %K Intelligence %K Meta-analyses %X Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders. %B Nature Genetics %V 50 %P 912 - 919 %8 Jan-07-2018 %G eng %U http://www.nature.com/articles/s41588-018-0152-6http://www.nature.com/articles/s41588-018-0152-6.pdfhttp://www.nature.com/articles/s41588-018-0152-6http://www.nature.com/articles/s41588-018-0152-6.pdf %N 7 %! Nat Genet %R 10.1038/s41588-018-0152-6 %0 Journal Article %J Nature Communications %D 2017 %T Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity. %A Joshi, Peter K %A Nicola Pirastu %A Kentistou, Katherine A %A Fischer, Krista %A Edith Hofer %A Schraut, Katharina E %A Clark, David W %A Nutile, Teresa %A Barnes, Catriona L K %A Paul Rhj Timmers %A Shen, Xia %A Gandin, Ilaria %A McDaid, Aaron F %A Hansen, Thomas Folkmann %A Gordon, Scott D %A Giulianini, Franco %A Boutin, Thibaud S %A Abdellaoui, Abdel %A Zhao, Wei %A Medina-Gomez, Carolina %A Traci M Bartz %A Trompet, Stella %A Leslie A Lange %A Raffield, Laura %A van der Spek, Ashley %A Galesloot, Tessel E %A Proitsi, Petroula %A Yanek, Lisa R %A Bielak, Lawrence F %A Payton, Antony %A Murgia, Federico %A Concas, Maria Pina %A Biino, Ginevra %A Tajuddin, Salman M %A Seppälä, Ilkka %A Amin, Najaf %A Boerwinkle, Eric %A Børglum, Anders D %A Campbell, Archie %A Ellen W Demerath %A Demuth, Ilja %A Jessica Faul %A Ford, Ian %A Gialluisi, Alessandro %A Gögele, Martin %A Graff, Mariaelisa %A Aroon Hingorani %A Jouke-Jan Hottenga %A Hougaard, David M %A Hurme, Mikko A %A Ikram, M Arfan %A Jylhä, Marja %A Kuh, Diana %A Ligthart, Lannie %A Lill, Christina M %A Lindenberger, Ulman %A Lumley, Thomas %A Mägi, Reedik %A Marques-Vidal, Pedro %A Sarah E Medland %A Lili Milani %A Nagy, Reka %A William E R Ollier %A Peyser, Patricia A %A Pramstaller, Peter P %A Ridker, Paul M %A Fernando Rivadeneira %A Ruggiero, Daniela %A Saba, Yasaman %A Schmidt, Reinhold %A Schmidt, Helena %A Slagboom, P Eline %A Smith, Blair H %A Smith, Jennifer A %A Sotoodehnia, Nona %A Steinhagen-Thiessen, Elisabeth %A van Rooij, Frank J A %A Verbeek, André L %A Vermeulen, Sita H %A Vollenweider, Peter %A Wang, Yunpeng %A Werge, Thomas %A Whitfield, John B %A Alan B Zonderman %A Lehtimäki, Terho %A Michele K Evans %A Pirastu, Mario %A Fuchsberger, Christian %A Bertram, Lars %A Pendleton, Neil %A Sharon L R Kardia %A Ciullo, Marina %A Becker, Diane M %A Wong, Andrew %A Psaty, Bruce M %A Cornelia M van Duijn %A Wilson, James G %A Jukema, J Wouter %A Lambertus A Kiemeney %A André G Uitterlinden %A Franceschini, Nora %A Kari E North %A David R Weir %A Andres Metspalu %A Dorret I Boomsma %A Caroline Hayward %A Daniel I Chasman %A Nicholas G Martin %A Sattar, Naveed %A Campbell, Harry %A Tõnu Esko %A Kutalik, Zoltán %A James F Wilson %K Alleles %K Body Mass Index %K Coronary Disease %K Education %K Genetic Predisposition to Disease %K Genome-Wide Association Study %K HLA-DQ alpha-Chains %K HLA-DRB1 Chains %K Humans %K Insulin Resistance %K Life Style %K Lipoprotein(a) %K Lipoproteins, HDL %K Longevity %K Lung Neoplasms %K Obesity %K Polymorphism, Single Nucleotide %K Smoking %K Socioeconomic factors %X

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

%B Nature Communications %V 8 %P 910 %G eng %N 1 %R 10.1038/s41467-017-00934-5 %0 Journal Article %J Nat Genet %D 2016 %T Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. %A Okbay, Aysu %A Baselmans, Bart M L %A De Neve, Jan-Emmanuel %A Turley, Patrick %A Nivard, Michel G %A Mark Alan Fontana %A Meddens, S Fleur W %A Richard Karlsson Linnér %A Cornelius A Rietveld %A Derringer, Jaime %A Gratten, Jacob %A Lee, James J %A Liu, Jimmy Z %A de Vlaming, Ronald %A Ahluwalia, Tarunveer S %A Buchwald, Jadwiga %A Cavadino, Alana %A Frazier-Wood, Alexis C %A Furlotte, Nicholas A %A Garfield, Victoria %A Geisel, Marie Henrike %A Gonzalez, Juan R %A Haitjema, Saskia %A Karlsson, Robert %A van der Laan, Sander W %A Ladwig, Karl-Heinz %A J. Lahti %A Sven J van der Lee %A Penelope A Lind %A Tian Liu %A Lindsay K Matteson %A Mihailov, Evelin %A Michael B Miller %A Minica, Camelia C %A Ilja M Nolte %A Dennis O Mook-Kanamori %A van der Most, Peter J %A Christopher J Oldmeadow %A Qian, Yong %A Olli T Raitakari %A Rawal, Rajesh %A Realo, Anu %A Rueedi, Rico %A Schmidt, Börge %A Albert Vernon Smith %A Stergiakouli, Evie %A Toshiko Tanaka %A Kent D Taylor %A Wedenoja, Juho %A Jürgen Wellmann %A Westra, Harm-Jan %A Willems, Sara M %A Wei Zhao %A Amin, Najaf %A Bakshi, Andrew %A Patricia A. Boyle %A Cherney, Samantha %A Cox, Simon R %A Gail Davies %A Davis, Oliver S P %A Ding, Jun %A Nese Direk %A Eibich, Peter %A Emeny, Rebecca T %A Fatemifar, Ghazaleh %A Jessica Faul %A Luigi Ferrucci %A Andreas J Forstner %A Gieger, Christian %A Gupta, Richa %A Tamara B Harris %A Harris, Juliette M %A Holliday, Elizabeth G %A Jouke-Jan Hottenga %A Philip L de Jager %A Marika A Kaakinen %A Kajantie, Eero %A Karhunen, Ville %A Kolcic, Ivana %A Kumari, Meena %A Lenore J Launer %A Lude L Franke %A Li-Gao, Ruifang %A Koini, Marisa %A Loukola, Anu %A Marques-Vidal, Pedro %A Grant W Montgomery %A Mosing, Miriam A %A Paternoster, Lavinia %A Pattie, Alison %A Katja E Petrovic %A Pulkki-Raback, Laura %A Quaye, Lydia %A Katri Räikkönen %A Rudan, Igor %A Rodney J Scott %A Jennifer A Smith %A Angelina R Sutin %A Trzaskowski, Maciej %A Anna A E Vinkhuyzen %A Lei Yu %A Zabaneh, Delilah %A John R. Attia %A David A Bennett %A Klaus Berger %A Bertram, Lars %A Dorret I Boomsma %A Snieder, Harold %A Chang, Shun-Chiao %A Francesco Cucca %A Ian J Deary %A Cornelia M van Duijn %A Johan G Eriksson %A Bültmann, Ute %A Eco J. C. de Geus %A Groenen, Patrick J F %A Gudnason, Vilmundur %A Hansen, Torben %A Catharina A Hartman %A Haworth, Claire M A %A Caroline Hayward %A Andrew C Heath %A Hinds, David A %A Hyppönen, Elina %A Iacono, William G %A Järvelin, Marjo-Riitta %A Jöckel, Karl-Heinz %A Kaprio, Jaakko %A Sharon L R Kardia %A Keltikangas-Järvinen, Liisa %A Kraft, Peter %A Laura D Kubzansky %A Lehtimäki, Terho %A Patrik K E Magnusson %A Nicholas G Martin %A McGue, Matt %A Andres Metspalu %A Melinda C Mills %A de Mutsert, Renée %A Oldehinkel, Albertine J %A Pasterkamp, Gerard %A Nancy L Pedersen %A Plomin, Robert %A Polasek, Ozren %A Power, Christine %A Rich, Stephen S %A Rosendaal, Frits R %A Hester M. den Ruijter %A Schlessinger, David %A Schmidt, Helena %A Svento, Rauli %A Schmidt, Reinhold %A Alizadeh, Behrooz Z %A Thorkild I. A. Sørensen %A Timothy Spector %A Andrew Steptoe %A Antonio Terracciano %A A. Roy Thurik %A Nicholas J Timpson %A Henning Tiemeier %A André G Uitterlinden %A Vollenweider, Peter %A Wagner, Gert G %A David R Weir %A Yang, Jian %A Dalton C Conley %A Hofman, Albert %A Johannesson, Magnus %A David I Laibson %A Sarah E Medland %A Meyer, Michelle N %A Pickrell, Joseph K %A Tõnu Esko %A Krueger, Robert F %A Jonathan P. Beauchamp %A Philipp D Koellinger %A Daniel J. Benjamin %A Bartels, Meike %A Cesarini, David %K Anxiety Disorders %K Bayes Theorem %K depression %K Genome-Wide Association Study %K Humans %K Neuroticism %K Phenotype %K Polymorphism, Single Nucleotide %X

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

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

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

%B Nat Genet %V 48 %P 1462-1472 %8 2016 Dec %G eng %N 12 %1 http://www.ncbi.nlm.nih.gov/pubmed/27798627?dopt=Abstract %R 10.1038/ng.3698 %0 Journal Article %J Nature %D 2016 %T Genome-wide association study identifies 74 loci associated with educational attainment. %A Okbay, Aysu %A Jonathan P. Beauchamp %A Mark Alan Fontana %A Lee, James J %A Pers, Tune H %A Cornelius A Rietveld %A Turley, Patrick %A Chen, Guo-Bo %A Emilsson, Valur %A Meddens, S Fleur W %A Oskarsson, Sven %A Pickrell, Joseph K %A Thom, Kevin %A Pascal N Timshel %A de Vlaming, Ronald %A Abdel Abdellaoui %A Ahluwalia, Tarunveer S %A Bacelis, Jonas %A Baumbach, Clemens %A Bjornsdottir, Gyda %A Brandsma, Johannes H %A Maria Pina Concas %A Derringer, Jaime %A Furlotte, Nicholas A %A Galesloot, Tessel E %A Giorgia G Girotto %A Gupta, Richa %A Hall, Leanne M %A Sarah E Harris %A Edith Hofer %A Horikoshi, Momoko %A Huffman, Jennifer E %A Kaasik, Kadri %A Ioanna Panagiota Kalafati %A Karlsson, Robert %A Kong, Augustine %A Lahti, Jari %A Sven J van der Lee %A Christiaan de Leeuw %A Penelope A Lind %A Lindgren, Karl-Oskar %A Tian Liu %A Mangino, Massimo %A Marten, Jonathan %A Mihailov, Evelin %A Michael B Miller %A van der Most, Peter J %A Christopher J Oldmeadow %A Payton, Antony %A Pervjakova, Natalia %A Wouter J Peyrot %A Qian, Yong %A Olli T Raitakari %A Rueedi, Rico %A Salvi, Erika %A Schmidt, Börge %A Schraut, Katharina E %A Jianxin Shi %A Albert Vernon Smith %A Poot, Raymond A %A St Pourcain, Beate %A Teumer, Alexander %A Thorleifsson, Gudmar %A Verweij, Niek %A Vuckovic, Dragana %A Jürgen Wellmann %A Westra, Harm-Jan %A Yang, Jingyun %A Wei Zhao %A Zhihong Zhu %A Alizadeh, Behrooz Z %A Amin, Najaf %A Bakshi, Andrew %A Baumeister, Sebastian E %A Biino, Ginevra %A Bønnelykke, Klaus %A Patricia A. Boyle %A Campbell, Harry %A Cappuccio, Francesco P %A Gail Davies %A De Neve, Jan-Emmanuel %A Deloukas, Panos %A Demuth, Ilja %A Ding, Jun %A Eibich, Peter %A Eisele, Lewin %A Eklund, Niina %A Jessica Faul %A Feitosa, Mary F %A Andreas J Forstner %A Gandin, Ilaria %A Gunnarsson, Bjarni %A Halldórsson, Bjarni V %A Tamara B Harris %A Andrew C Heath %A Lynne J Hocking %A Holliday, Elizabeth G %A Homuth, Georg %A Horan, Michael A %A Jouke-Jan Hottenga %A Philip L de Jager %A Joshi, Peter K %A Jugessur, Astanand %A Marika A Kaakinen %A Kähönen, Mika %A Kanoni, Stavroula %A Keltigangas-Järvinen, Liisa %A Lambertus A Kiemeney %A Kolcic, Ivana %A Koskinen, Seppo %A Kraja, Aldi T %A Kroh, Martin %A Kutalik, Zoltán %A Latvala, Antti %A Lenore J Launer %A Lebreton, Maël P %A Douglas F Levinson %A Paul Lichtenstein %A Lichtner, Peter %A David C Liewald %A Loukola, Anu %A Pamela A F Madden %A Mägi, Reedik %A Mäki-Opas, Tomi %A Riccardo E Marioni %A Marques-Vidal, Pedro %A Meddens, Gerardus A %A McMahon, George %A Meisinger, Christa %A Meitinger, Thomas %A Milaneschi, Yusplitri %A Lili Milani %A Grant W Montgomery %A Myhre, Ronny %A Nelson, Christopher P %A Nyholt, Dale R %A William E R Ollier %A Aarno Palotie %A Paternoster, Lavinia %A Nancy L Pedersen %A Katja E Petrovic %A David J Porteous %A Katri Räikkönen %A Ring, Susan M %A Robino, Antonietta %A Rostapshova, Olga %A Rudan, Igor %A Rustichini, Aldo %A Veikko Salomaa %A Sanders, Alan R %A Sarin, Antti-Pekka %A Schmidt, Helena %A Rodney J Scott %A Smith, Blair H %A Jennifer A Smith %A Staessen, Jan A %A Steinhagen-Thiessen, Elisabeth %A Strauch, Konstantin %A Antonio Terracciano %A Tobin, Martin D %A Ulivi, Sheila %A Vaccargiu, Simona %A Quaye, Lydia %A van Rooij, Frank J A %A Venturini, Cristina %A Anna A E Vinkhuyzen %A Völker, Uwe %A Völzke, Henry %A Vonk, Judith M %A Vozzi, Diego %A Waage, Johannes %A Erin B Ware %A Gonneke Willemsen %A John R. Attia %A David A Bennett %A Klaus Berger %A Bertram, Lars %A Bisgaard, Hans %A Dorret I Boomsma %A Ingrid B Borecki %A Bültmann, Ute %A Chabris, Christopher F %A Francesco Cucca %A Cusi, Daniele %A Ian J Deary %A George Dedoussis %A Cornelia M van Duijn %A Johan G Eriksson %A Franke, Barbara %A Lude L Franke %A Paolo P. Gasparini %A Gejman, Pablo V %A Gieger, Christian %A Hans-Jörgen Grabe %A Gratten, Jacob %A Groenen, Patrick J F %A Gudnason, Vilmundur %A van der Harst, Pim %A Caroline Hayward %A Hinds, David A %A Hoffmann, Wolfgang %A Hyppönen, Elina %A Iacono, William G %A Jacobsson, Bo %A Järvelin, Marjo-Riitta %A Jöckel, Karl-Heinz %A Kaprio, Jaakko %A Sharon L R Kardia %A Lehtimäki, Terho %A Lehrer, Steven F %A Patrik K E Magnusson %A Nicholas G Martin %A McGue, Matt %A Andres Metspalu %A Pendleton, Neil %A Brenda W J H Penninx %A Markus Perola %A Nicola Pirastu %A Pirastu, Mario %A Polasek, Ozren %A Posthuma, Danielle %A Power, Christine %A Province, Michael A %A Nilesh J Samani %A Schlessinger, David %A Schmidt, Reinhold %A Thorkild I. A. Sørensen %A Timothy Spector %A Stefansson, Kari %A Thorsteinsdottir, Unnur %A A. Roy Thurik %A Nicholas J Timpson %A Henning Tiemeier %A Tung, Joyce Y %A André G Uitterlinden %A Vitart, Veronique %A Vollenweider, Peter %A David R Weir %A James F Wilson %A Alan F Wright %A Dalton C Conley %A Krueger, Robert F %A George Davey Smith %A Hofman, Albert %A David I Laibson %A Sarah E Medland %A Meyer, Michelle N %A Yang, Jian %A Johannesson, Magnus %A Peter M Visscher %A Tõnu Esko %A Philipp D Koellinger %A Cesarini, David %A Daniel J. Benjamin %K Alzheimer's disease %K Bipolar Disorder %K Cognitive Ability %K Education %K Fetus %K Genome-Wide Association Study %K Humans %K Molecular Sequence Annotation %K Polymorphism, Single Nucleotide %K Schizophrenia %K United Kingdom %X

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

%B Nature %V 533 %P 539-42 %8 2016 05 26 %G eng %N 7604 %1 http://www.ncbi.nlm.nih.gov/pubmed/27225129?dopt=Abstract %R 10.1038/nature17671 %0 Journal Article %J Nature %D 2015 %T Genetic studies of body mass index yield new insights for obesity biology. %A Locke, Adam E %A Kahali, Bratati %A Berndt, Sonja I %A Justice, Anne E %A Pers, Tune H %A Day, Felix R %A Powell, Corey %A Vedantam, Sailaja %A Buchkovich, Martin L %A Yang, Jian %A Croteau-Chonka, Damien C %A Tõnu Esko %A Fall, Tove %A Ferreira, Teresa %A Gustafsson, Stefan %A Kutalik, Zoltán %A Luan, Jian'an %A Mägi, Reedik %A Randall, Joshua C %A Thomas W Winkler %A Andrew R Wood %A Workalemahu, Tsegaselassie %A Jessica Faul %A Jennifer A Smith %A Jing Hua Zhao %A Wei Zhao %A Chen, Jin %A Rudolf Ferhmann %A Hedman, Åsa K %A Karjalainen, Juha %A Schmidt, Ellen M %A Absher, Devin %A Amin, Najaf %A Anderson, Denise %A Beekman, Marian %A Bolton, Jennifer L %A Bragg-Gresham, Jennifer L %A Buyske, Steven %A Demirkan, Ayse %A Deng, Guohong %A Georg B Ehret %A Feenstra, Bjarke %A Feitosa, Mary F %A Fischer, Krista %A Goel, Anuj %A Gong, Jian %A Jackson, Anne U %A Kanoni, Stavroula %A Kleber, Marcus E %A Kristiansson, Kati %A Lim, Unhee %A Lotay, Vaneet %A Mangino, Massimo %A Irene Mateo Leach %A Medina-Gomez, Carolina %A Sarah E Medland %A Michael A Nalls %A Palmer, Cameron D %A Pasko, Dorota %A Pechlivanis, Sonali %A Peters, Marjolein J %A Prokopenko, Inga %A Shungin, Dmitry %A Stančáková, Alena %A Strawbridge, Rona J %A Yun Ju Sung %A Toshiko Tanaka %A Teumer, Alexander %A Trompet, Stella %A van der Laan, Sander W %A van Setten, Jessica %A Jana V. van Vliet-Ostaptchouk %A Wang, Zhaoming %A Yengo, Loic %A Zhang, Weihua %A Isaacs, Aaron %A Albrecht, Eva %A Ärnlöv, Johan %A Arscott, Gillian M %A Attwood, Antony P %A Bandinelli, Stefania %A Barrett, Amy %A Bas, Isabelita N %A Bellis, Claire %A Bennett, Amanda J %A Berne, Christian %A Blagieva, Roza %A Blüher, Matthias %A Böhringer, Stefan %A Bonnycastle, Lori L %A Böttcher, Yvonne %A Boyd, Heather A %A Bruinenberg, Marcel %A Caspersen, Ida H %A Yii-Der I Chen %A Robert Clark %A Daw, E Warwick %A de Craen, Anton J M %A Delgado, Graciela %A Dimitriou, Maria %A Doney, Alex S F %A Eklund, Niina %A Estrada, Karol %A Eury, Elodie %A Folkersen, Lasse %A Fraser, Ross M %A Melissa E Garcia %A Geller, Frank %A Giedraitis, Vilmantas %A Gigante, Bruna %A Alan S Go %A Golay, Alain %A Goodall, Alison H %A Gordon, Scott D %A Gorski, Mathias %A Hans-Jörgen Grabe %A Grallert, Harald %A Grammer, Tanja B %A Gräßler, Jürgen %A Grönberg, Henrik %A Groves, Christopher J %A Gusto, Gaëlle %A Jeffrey Haessler %A Hall, Per %A Haller, Toomas %A Hallmans, Göran %A Catharina A Hartman %A Hassinen, Maija %A Caroline Hayward %A Heard-Costa, Nancy L %A Helmer, Quinta %A Hengstenberg, Christian %A Oddgeir L Holmen %A Jouke-Jan Hottenga %A James, Alan L %A Janina Jeff %A Johansson, Åsa %A Jolley, Jennifer %A Juliusdottir, Thorhildur %A Kinnunen, Leena %A Koenig, Wolfgang %A Koskenvuo, Markku %A Kratzer, Wolfgang %A Laitinen, Jaana %A Lamina, Claudia %A Leander, Karin %A Lee, Nanette R %A Lichtner, Peter %A Lars Lind %A Lindström, Jaana %A Ken Sin Lo %A Lobbens, Stéphane %A Lorbeer, Roberto %A Lu, Yingchang %A Mach, François %A Patrik K E Magnusson %A Mahajan, Anubha %A McArdle, Wendy L %A McLachlan, Stela %A Menni, Cristina %A Merger, Sigrun %A Mihailov, Evelin %A Lili Milani %A Moayyeri, Alireza %A Monda, Keri L %A Morken, Mario A %A Mulas, Antonella %A Müller, Gabriele %A Müller-Nurasyid, Martina %A Musk, Arthur W %A Nagaraja, Ramaiah %A Markus M Nöthen %A Ilja M Nolte %A Pilz, Stefan %A Nigel W Rayner %A Renstrom, Frida %A Rettig, Rainer %A Ried, Janina S %A Ripke, Stephan %A Neil R Robertson %A Rose, Lynda M %A Sanna, Serena %A Scharnagl, Hubert %A Scholtens, Salome %A Schumacher, Fredrick R %A Scott, William R %A Seufferlein, Thomas %A Jianxin Shi %A Albert Vernon Smith %A Smolonska, Joanna %A Stanton, Alice V %A Steinthorsdottir, Valgerdur %A Kathleen E Stirrups %A Heather M Stringham %A Sundström, Johan %A Swertz, Morris A %A Swift, Amy J %A Syvänen, Ann-Christine %A Tan, Sian-Tsung %A Bamidele O Tayo %A Thorand, Barbara %A Thorleifsson, Gudmar %A Tyrer, Jonathan P %A Uh, Hae-Won %A Vandenput, Liesbeth %A Verhulst, Frank C %A Vermeulen, Sita H %A Verweij, Niek %A Vonk, Judith M %A Lindsay L Waite %A Warren, Helen R %A Dawn M Waterworth %A Michael N Weedon %A Wilkens, Lynne R %A Willenborg, Christina %A Wilsgaard, Tom %A Wojczynski, Mary K %A Wong, Andrew %A Alan F Wright %A Zhang, Qunyuan %A Brennan, Eoin P %A Murim Choi %A Dastani, Zari %A Alexander W Drong %A Eriksson, Per %A Franco-Cereceda, Anders %A Gådin, Jesper R %A Gharavi, Ali G %A Goddard, Michael E %A Handsaker, Robert E %A Huang, Jinyan %A Karpe, Fredrik %A Kathiresan, Sekar %A Keildson, Sarah %A Kiryluk, Krzysztof %A Kubo, Michiaki %A Lee, Jong-Young %A Liang, Liming %A Lifton, Richard P %A Ma, Baoshan %A McCarroll, Steven A %A McKnight, Amy J %A Min, Josine L %A Moffatt, Miriam F %A Grant W Montgomery %A Joanne M Murabito %A Nicholson, George %A Nyholt, Dale R %A Okada, Yukinori %A Perry, John R B %A Dorajoo, Rajkumar %A Reinmaa, Eva %A Salem, Rany M %A Sandholm, Niina %A Scott, Robert A %A Stolk, Lisette %A Takahashi, Atsushi %A Tanaka, Toshihiro %A Ferdinand M van 't Hooft %A Anna A E Vinkhuyzen %A Westra, Harm-Jan %A Wei Zhang %A Krina T Zondervan %A Andrew C Heath %A Arveiler, Dominique %A Bakker, Stephan J L %A Beilby, John %A Bergman, Richard N %A Blangero, John %A Bovet, Pascal %A Campbell, Harry %A Caulfield, Mark J %A Cesana, Giancarlo %A Chakravarti, Aravinda %A Daniel I Chasman %A Chines, Peter S %A Collins, Francis S %A Crawford, Dana C %A Cupples, L Adrienne %A Cusi, Daniele %A Danesh, John %A de Faire, Ulf %A Hester M den Ruijter %A Dominiczak, Anna F %A Erbel, Raimund %A Erdmann, Jeanette %A Johan G Eriksson %A Farrall, Martin %A Felix, Stephan B %A Ferrannini, Ele %A Ferrières, Jean %A Ford, Ian %A Forouhi, Nita G %A Forrester, Terrence %A Franco, Oscar H %A Gansevoort, Ron T %A Gejman, Pablo V %A Gieger, Christian %A Gottesman, Omri %A Gudnason, Vilmundur %A Gyllensten, Ulf %A Hall, Alistair S %A Tamara B Harris %A Andrew T Hattersley %A Hicks, Andrew A %A Hindorff, Lucia A %A Aroon Hingorani %A Hofman, Albert %A Homuth, Georg %A Hovingh, G Kees %A Humphries, Steve E %A Hunt, Steven C %A Hyppönen, Elina %A Illig, Thomas %A Jacobs, Kevin B %A Järvelin, Marjo-Riitta %A Jöckel, Karl-Heinz %A Johansen, Berit %A Jousilahti, Pekka %A Jukema, J Wouter %A Jula, Antti M %A Kaprio, Jaakko %A Kastelein, John J P %A Keinanen-Kiukaanniemi, Sirkka M %A Lambertus A Kiemeney %A Knekt, Paul %A Kooner, Jaspal S %A Charles Kooperberg %A Kovacs, Peter %A Kraja, Aldi T %A Kumari, Meena %A Kuusisto, Johanna %A Lakka, Timo A %A Langenberg, Claudia %A Loic Le Marchand %A Lehtimäki, Terho %A Lyssenko, Valeriya %A Männistö, Satu %A Marette, André %A Matise, Tara C %A McKenzie, Colin A %A McKnight, Barbara %A Moll, Frans L %A Morris, Andrew D %A Morris, Andrew P %A Murray, Jeffrey C %A Nelis, Mari %A Ohlsson, Claes %A Oldehinkel, Albertine J %A Ong, Ken K %A Pamela A F Madden %A Pasterkamp, Gerard %A Peden, John F %A Peters, Annette %A Postma, Dirkje S %A Pramstaller, Peter P %A Price, Jackie F %A Qi, Lu %A Olli T Raitakari %A Rankinen, Tuomo %A Rao, D C %A Rice, Treva K %A Ridker, Paul M %A Rioux, John D %A Ritchie, Marylyn D %A Rudan, Igor %A Veikko Salomaa %A Nilesh J Samani %A Saramies, Jouko %A Sarzynski, Mark A %A Schunkert, Heribert %A Schwarz, Peter E H %A Peter Sever %A Alan R Shuldiner %A Sinisalo, Juha %A Stolk, Ronald P %A Strauch, Konstantin %A Tönjes, Anke %A Trégouët, David-Alexandre %A Tremblay, Angelo %A Tremoli, Elena %A Virtamo, Jarmo %A Vohl, Marie-Claude %A Völker, Uwe %A Waeber, Gérard %A Gonneke Willemsen %A Witteman, Jacqueline C %A Zillikens, M Carola %A Adair, Linda S %A Amouyel, Philippe %A Asselbergs, Folkert W %A Assimes, Themistocles L %A Bochud, Murielle %A Boehm, Bernhard O %A Boerwinkle, Eric %A Bornstein, Stefan R %A Erwin P Bottinger %A Bouchard, Claude %A Cauchi, Stéphane %A Chambers, John C %A Chanock, Stephen J %A Cooper, Richard S %A de Bakker, Paul I W %A George Dedoussis %A Luigi Ferrucci %A Franks, Paul W %A Froguel, Philippe %A Leif C Groop %A Christopher A Haiman %A Hamsten, Anders %A Hui, Jennie %A Hunter, David J %A Hveem, Kristian %A Kaplan, Robert C %A Mika Kivimäki %A Kuh, Diana %A Laakso, Markku %A Yongmei Liu %A Nicholas G Martin %A März, Winfried %A Melbye, Mads %A Andres Metspalu %A Moebus, Susanne %A Munroe, Patricia B %A Njølstad, Inger %A Ben A Oostra %A Palmer, Colin N A %A Nancy L Pedersen %A Markus Perola %A Pérusse, Louis %A Peters, Ulrike %A Power, Chris %A Quertermous, Thomas %A Rauramaa, Rainer %A Fernando Rivadeneira %A Saaristo, Timo E %A Saleheen, Danish %A Sattar, Naveed %A Eric E Schadt %A Schlessinger, David %A Eline P Slagboom %A Snieder, Harold %A Timothy Spector %A Thorsteinsdottir, Unnur %A Stumvoll, Michael %A Tuomilehto, Jaakko %A André G Uitterlinden %A Uusitupa, Matti %A van der Harst, Pim %A Walker, Mark %A Wallaschofski, Henri %A Wareham, Nicholas J %A Watkins, Hugh %A David R Weir %A Wichmann, H-Erich %A James F Wilson %A Zanen, Pieter %A Ingrid B Borecki %A Deloukas, Panos %A Caroline S Fox %A Iris M Heid %A Jeff O'Connell %A David P Strachan %A Stefansson, Kari %A Cornelia M van Duijn %A Gonçalo R Abecasis %A Lude L Franke %A Timothy M Frayling %A McCarthy, Mark I %A Peter M Visscher %A Scherag, Andre %A Willer, Cristen J %A Boehnke, Michael %A Mohlke, Karen L %A Lindgren, Cecilia M %A Beckmann, Jacques S %A Barroso, Inês %A Kari E North %A Ingelsson, Erik %A Joel N Hirschhron %A Ruth J F Loos %A Elizabeth K Speliotes %K Age Factors %K BMI %K Continental Population Groups %K Energy Metabolism %K Europe %K Female %K Genome-Wide Association Study %K Glutamic Acid %K Humans %K Insulin %K Male %K Obesity %K Polymorphism, Single Nucleotide %K Quantitative Trait Loci %K Synapses %X

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

%B Nature %V 518 %P 197-206 %8 2015 Feb 12 %G eng %N 7538 %1 http://www.ncbi.nlm.nih.gov/pubmed/25673413?dopt=Abstract %R 10.1038/nature14177 %0 Journal Article %J Science %D 2013 %T GWAS of 126,559 individuals identifies genetic variants associated with educational attainment. %A Cornelius A Rietveld %A Sarah E Medland %A Derringer, Jaime %A Yang, Jian %A Tõnu Esko %A Martin, Nicolas W %A Westra, Harm-Jan %A Shakhbazov, Konstantin %A Abdel Abdellaoui %A Agrawal, Arpana %A Albrecht, Eva %A Alizadeh, Behrooz Z %A Amin, Najaf %A Barnard, John %A Baumeister, Sebastian E %A Benke, Kelly S %A Bielak, Lawrence F %A Boatman, Jeffrey A %A Patricia A. Boyle %A Gail Davies %A Christiaan de Leeuw %A Eklund, Niina %A Daniel S Evans %A Rudolf Ferhmann %A Fischer, Krista %A Gieger, Christian %A Gjessing, Håkon K %A Hägg, Sara %A Harris, Jennifer R %A Caroline Hayward %A Holzapfel, Christina %A Carla A Ibrahim-Verbaas %A Ingelsson, Erik %A Jacobsson, Bo %A Joshi, Peter K %A Jugessur, Astanand %A Marika A Kaakinen %A Kanoni, Stavroula %A Karjalainen, Juha %A Kolcic, Ivana %A Kristiansson, Kati %A Kutalik, Zoltán %A J. Lahti %A Lee, Sang H %A Lin, Peng %A Penelope A Lind %A Yongmei Liu %A Kurt Lohman %A Loitfelder, Marisa %A McMahon, George %A Vidal, Pedro Marques %A Osorio Meirelles %A Lili Milani %A Myhre, Ronny %A Nuotio, Marja-Liisa %A Christopher J Oldmeadow %A Katja E Petrovic %A Wouter J Peyrot %A Polasek, Ozren %A Quaye, Lydia %A Reinmaa, Eva %A Rice, John P %A Rizzi, Thais S %A Schmidt, Helena %A Schmidt, Reinhold %A Albert Vernon Smith %A Jennifer A Smith %A Toshiko Tanaka %A Antonio Terracciano %A van der Loos, Matthijs J H M %A Vitart, Veronique %A Völzke, Henry %A Jürgen Wellmann %A Lei Yu %A Wei Zhao %A Allik, Jüri %A John R. Attia %A Bandinelli, Stefania %A Bastardot, François %A Jonathan P. Beauchamp %A David A Bennett %A Klaus Berger %A Laura Bierut %A Dorret I Boomsma %A Bültmann, Ute %A Campbell, Harry %A Chabris, Christopher F %A Cherkas, Lynn %A Chung, Mina K %A Francesco Cucca %A de Andrade, Mariza %A Philip L de Jager %A De Neve, Jan-Emmanuel %A Ian J Deary %A George Dedoussis %A Deloukas, Panos %A Dimitriou, Maria %A Guðny Eiríksdóttir %A Elderson, Martin F %A Johan G Eriksson %A Jessica Faul %A Luigi Ferrucci %A Melissa E Garcia %A Grönberg, Henrik %A Guðnason, Vilmundur %A Hall, Per %A Harris, Juliette M %A Tamara B Harris %A Nicholas D Hastie %A Andrew C Heath %A Dena G Hernandez %A Hoffmann, Wolfgang %A Hofman, Adriaan %A Holle, Rolf %A Holliday, Elizabeth G %A Jouke-Jan Hottenga %A Iacono, William G %A Illig, Thomas %A Järvelin, Marjo-Riitta %A Kähönen, Mika %A Kaprio, Jaakko %A Kirkpatrick, Robert M %A Kowgier, Matthew %A Latvala, Antti %A Lenore J Launer %A Lawlor, Debbie A %A Lehtimäki, Terho %A Li, Jingmei %A Paul Lichtenstein %A Lichtner, Peter %A David C Liewald %A Pamela A F Madden %A Patrik K E Magnusson %A Mäkinen, Tomi E %A Masala, Marco %A McGue, Matt %A Andres Metspalu %A Mielck, Andreas %A Michael B Miller %A Grant W Montgomery %A Mukherjee, Sutapa %A Nyholt, Dale R %A Ben A Oostra %A Palmer, Lyle J %A Aarno Palotie %A Brenda W J H Penninx %A Markus Perola %A Peyser, Patricia A %A Preisig, Martin %A Katri Räikkönen %A Olli T Raitakari %A Realo, Anu %A Ring, Susan M %A Ripatti, Samuli %A Fernando Rivadeneira %A Rudan, Igor %A Rustichini, Aldo %A Veikko Salomaa %A Sarin, Antti-Pekka %A Schlessinger, David %A Rodney J Scott %A Snieder, Harold %A St Pourcain, Beate %A John M Starr %A Sul, Jae Hoon %A Surakka, Ida %A Svento, Rauli %A Teumer, Alexander %A Henning Tiemeier %A van Rooij, Frank J A %A Van Wagoner, David R %A Vartiainen, Erkki %A Viikari, Jorma %A Vollenweider, Peter %A Vonk, Judith M %A Waeber, Gérard %A David R Weir %A Wichmann, H-Erich %A Elisabeth Widen %A Gonneke Willemsen %A James F Wilson %A Alan F Wright %A Dalton C Conley %A Davey-Smith, George %A Lude L Franke %A Groenen, Patrick J F %A Hofman, Albert %A Johannesson, Magnus %A Sharon L R Kardia %A Krueger, Robert F %A David I Laibson %A Nicholas G Martin %A Meyer, Michelle N %A Posthuma, Danielle %A A. Roy Thurik %A Nicholas J Timpson %A André G Uitterlinden %A Cornelia M van Duijn %A Peter M Visscher %A Daniel J. Benjamin %A Cesarini, David %A Philipp D Koellinger %K Cognition %K Educational Status %K Endophenotypes %K Female %K Genetic Loci %K Genome-Wide Association Study %K Humans %K Male %K Multifactorial Inheritance %K Polymorphism, Single Nucleotide %X

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

%B Science %V 340 %P 1467-71 %8 2013 Jun 21 %G eng %N 6139 %1 http://www.ncbi.nlm.nih.gov/pubmed/23722424?dopt=Abstract %R 10.1126/science.1235488