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Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals

Nature Genetics volume 50, pages 1112–1121 (2018)Cite this article

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Abstract

Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11–13% of the variance in educational attainment and 7–10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.

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Fig. 1: Manhattan Plot for GWAS of EduYears.
Fig. 2: Sign concordance in within-family association analyses.
Fig. 3: Tissue-specific expression of genes in DEPICT-defined loci.
Fig. 4: Prediction Accuracy.

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Acknowledgements

This research was carried out under the auspices of the Social Science Genetic Association Consortium (SSGAC). The research has also been conducted using the UK Biobank Resource under application numbers 11425 and 12512. We acknowledge the Swedish Twin Registry for access to data. The Swedish Twin Registry is managed by the Karolinska Institutet and receives funding through the Swedish Research Council under the grant number 2017-00641. This study was supported by funding from the Ragnar Söderberg Foundation (E9/11, E42/15), the Swedish Research Council (421-2013-1061), The Jan Wallander and Tom Hedelius Foundation, an ERC Consolidator Grant (647648 EdGe), the Pershing Square Fund of the Foundations of Human Behavior, The Open Philanthropy Project (2016-152872), and the NIA/NIH through grants P01-AG005842, P01-AG005842-20S2, P30-AG012810 and T32-AG000186-23 to N.B.E.R. and R01-AG042568 to U.S.C. A full list of acknowledgments is provided in the Supplementary Note.

Author information

Author notes

  1. These authors contributed equally: James J. Lee, Robbee Wedow, Aysu Okbay.

  2. These authors jointly supervised this work: Patrick Turley, Peter M. Visscher, Daniel J. Benjamin, David Cesarini.

  3. A list of members and affiliations appears at the end of the paper.

  4. A list of members and affiliations appears in the Supplementary Information.

Authors and Affiliations

  1. Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA

    James J. Lee, Emily A. Willoughby, James J. Lee, Michael B. Miller, William G. Iacono, Matt McGue & Robert F. Krueger

  2. Department of Sociology, University of Colorado Boulder, Boulder, CO, USA

    Robbee Wedow & Jason D. Boardman

  3. Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA

    Robbee Wedow & Jason D. Boardman

  4. Institute of Behavioral Science, University of Colorado Boulder, Boulder, CO, USA

    Robbee Wedow & Jason D. Boardman

  5. Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

    Aysu Okbay, Richard Karlsson Linnér, Aysu Okbay, S. Fleur W. Meddens, Christiaan de Leeuw, Danielle Posthuma, Philipp D. Koellinger & Philipp D. Koellinger

  6. Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

    Aysu Okbay, Richard Karlsson Linnér, Aysu Okbay, Philipp D. Koellinger & Philipp D. Koellinger

  7. Department of Economics, Harvard University, Cambridge, MA, USA

    Edward Kong, Omeed Maghzian, Peter Bowers, Chanwook Lee, Hui Li, Olga Rostapshova, David I. Laibson & David I. Laibson

  8. Department of Sociology, Harvard University, Cambridge, MA, USA

    Meghan Zacher

  9. Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA

    Tuan Anh Nguyen-Viet, Mark Alan Fontana, Tushar Kundu, Ruoxi Li, Rebecca Royer, Mark Alan Fontana, Daniel J. Benjamin, Chelsea Watson & Daniel J. Benjamin

  10. Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia

    Julia Sidorenko, Loïc Yengo, Jian Yang, Peter M. Visscher, Kathryn E. Kemper, Yang Wu, Zhili Zheng, Matthew R. Robinson, Jian Yang & Peter M. Visscher

  11. Estonian Genome Center, University of Tartu, Tartu, Estonia

    Julia Sidorenko, Evelin Mihailov, Natalia Pervjakova, Reedik Mägi, Lili Milani, Andres Metspalu, Markus Perola, Tõnu Esko, Maris Alver, Reedik Mägi, Andres Metspalu, Lili Milani & Tõnu Esko

  12. Institute for Behavior and Biology, Erasmus University Rotterdam, Rotterdam, The Netherlands

    Richard Karlsson Linnér, Cornelius A. Rietveld, S. Fleur W. Meddens, Ronald de Vlaming, A. Roy Thurik, Philipp D. Koellinger & Philipp D. Koellinger

  13. Center for the Advancement of Value in Musculoskeletal Care, Hospital for Special Surgery, New York, NY, USA

    Mark Alan Fontana & Mark Alan Fontana

  14. The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark

    Pascal N. Timshel, Tune H. Pers, Pascal Timshel, Tarunveer S. Ahluwalia, Thorkild I. A. Sørensen & Tune H. Pers

  15. Statens Serum Institut, Department of Epidemiology Research, Copenhagen, Denmark

    Pascal N. Timshel, Tune H. Pers, Pascal Timshel & Tune H. Pers

  16. Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA

    Raymond K. Walters, Patrick Turley, Aarno Palotie & Patrick Turley

  17. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Raymond K. Walters, Patrick Turley, Aarno Palotie & Patrick Turley

  18. Institute for Social and Economic Research, University of Essex, Colchester, UK

    Yanchun Bao, Pamela Herd & Meena Kumari

  19. Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK

    Katharina E. Schraut, Harry Campbell, Peter K. Joshi, Igor Rudan, Ozren Polasek, James F. Wilson, David W. Clark, Peter K. Joshi, Harry Campbell, Melissa C. Smart & James F. Wilson

  20. MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK

    Felix R. Day, Claudia Langenberg, Jing Hua Zhao, Jian’an Luan, Ken K. Ong, John R. B. Perry & Nicholas J. Wareham

  21. 23andMe, Inc., Mountain View, CA, USA

    Michelle Agee, Babak Alipanahi, Adam Auton, Robert K. Bell, Katarzyna Bryc, Sarah L. Elson, Pierre Fontanillas, David A. Hinds, Jennifer C. McCreight., Karen E. Huber, Nadia K. Litterman, Matthew H. McIntyre, Joanna L. Mountain, Elizabeth S. Noblin, Carrie A. M. Northover, Steven J. Pitts, J. Fah Sathirapongsasuti, Olga V. Sazonova, Janie F. Shelton, Suyash Shringarpure, Chao Tian, Vladimir Vacic, Catherine H. Wilson, Nicholas A. Furlotte, David A. Hinds, Joyce Y. Tung, Nicholas A. Furlotte, Aaron Kleinman & Joyce Y. Tung

  22. Institute of Social and Preventive Medicine, University Hospital of Lausanne, Lausanne, Switzerland

    Peter K. Joshi & Peter K. Joshi

  23. BrainWorkup, LLC, Santa Monica, CA, USA

    Joey W. Trampush

  24. Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Joey W. Trampush

  25. Department of Biomedical and Translational Informatics, Geisinger Health System, Danville, PA, USA

    Shefali Setia Verma & Marylyn D. Ritchie

  26. Institute of Mental Health, Singapore, Singapore

    Max Lam

  27. Genome Institute, Singapore, Singapore

    Max Lam

  28. The Eye Hospital, School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, China

    Zhili Zheng

  29. Department of Sociology, Stanford University, Stanford, CA, USA

    Jeremy Freese

  30. Department of Sociology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Kathleen Mullan Harris

  31. Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Kathleen Mullan Harris

  32. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK

    Jennifer E. Huffman, Jonathan Marten, Caroline Hayward, Veronique Vitart, James F. Wilson, Alan F. Wright, Caroline Hayward & James F. Wilson

  33. La Follette School of Public Affairs, University of Wisconsin-Madison, Madison, WI, USA

    Pamela Herd

  34. Departments of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY, USA

    Todd Lencz & Anil K. Malhotra

  35. Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA

    Todd Lencz & Anil K. Malhotra

  36. Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, CA, USA

    Todd Lencz & Anil K. Malhotra

  37. Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia

    Andres Metspalu & Andres Metspalu

  38. Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK

    Sarah E. Harris, David J. Porteous & David J. Porteous

  39. Division of Population Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK

    Blair H. Smith & Blair H. Smith

  40. Medical Research Institute, University of Dundee, Dundee, UK

    Blair H. Smith & Blair H. Smith

  41. Department of Economics, University of Toronto, Toronto, Ontario, Canada

    Jonathan P. Beauchamp, Riccardo E. Marioni & Jonathan P. Beauchamp

  42. Department of Sociology, Princeton University, Princeton, NJ, USA

    Dalton C. Conley & Dalton C. Conley

  43. School of Policy Studies, Queen’s University, Kingston, Ontario, Canada

    Steven F. Lehrer & Steven F. Lehrer

  44. Department of Economics, New York University Shanghai, Pudong, Shanghai, China

    Steven F. Lehrer & Steven F. Lehrer

  45. National Bureau of Economic Research, Cambridge, MA, USA

    Steven F. Lehrer, David Cesarini, Daniel J. Benjamin, Steven F. Lehrer, Daniel J. Benjamin & David Cesarini

  46. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    Robert Karlsson, Paul Lichtenstein, Nancy L. Pedersen, Patrik K. E. Magnusson & Patrik K. E. Magnusson

  47. Department of Government, Uppsala University, Uppsala, Sweden

    Sven Oskarsson, Karl-Oskar Lindgren & Sven Oskarsson

  48. Department of Computational Biology, University of Lausanne, Lausanne, Switzerland

    Matthew R. Robinson

  49. Department of Economics, New York University, New York, NY, USA

    Kevin Thom, David Cesarini, Kevin Thom & David Cesarini

  50. Autism and Developmental Medicine Institute, Geisinger Health System, Lewisburg, PA, USA

    Christopher F. Chabris & Christopher F. Chabris

  51. Center for Translational Bioethics and Health Care Policy, Geisinger Health System, Danville, PA, USA

    Michelle N. Meyer & Michelle N. Meyer

  52. Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia

    Guo-Bo Chen, Zhihong Zhu, Andrew Bakshi, Anna A. E. Vinkhuyzen, Jacob Gratten, Jian Yang, Peter M. Visscher, Jian Yang & Peter M. Visscher

  53. Department of Economics, Stockholm School of Economics, Stockholm, Sweden

    Magnus Johannesson & Magnus Johannesson

  54. Department of Economics, University of Southern California, Los Angeles, CA, USA

    Daniel J. Benjamin & Daniel J. Benjamin

  55. Center for Experimental Social Science, New York University, New York, NY, USA

    David Cesarini & David Cesarini

  56. Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, The Netherlands

    Cornelius A. Rietveld, Ronald de Vlaming & A. Roy Thurik

  57. Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands

    Cornelius A. Rietveld, Ronald de Vlaming, Sven J. van der Lee, Najaf Amin, Frank J. A. van Rooij, Cornelia M. van Duijn, Henning Tiemeier, André G. Uitterlinden & Albert Hofman

  58. Icelandic Heart Association, Kopavogur, Iceland

    Valur Emilsson, Albert V. Smith & Vilmundur Gudnason

  59. Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavík, Iceland

    Valur Emilsson

  60. Amsterdam Business School, University of Amsterdam, Amsterdam, The Netherlands

    S. Fleur W. Meddens & Maël P. Lebreton

  61. New York Genome Center, New York, NY, USA

    Joseph K. Pickrell

  62. Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands

    Abdel Abdellaoui, Jouke-Jan Hottenga, Gonneke Willemsen & Dorret I. Boomsma

  63. COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark

    Tarunveer S. Ahluwalia, Klaus Bønnelykke, Johannes Waage & Hans Bisgaard

  64. Steno Diabetes Center, Gentofte, Denmark

    Tarunveer S. Ahluwalia & Johannes Waage

  65. Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden

    Jonas Bacelis & Bo Jacobsson

  66. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

    Clemens Baumbach & Christian Gieger

  67. Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

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  68. deCODE Genetics/Amgen Inc., Reykjavík, Iceland

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  70. Istituto di Ricerca Genetica e Biomedica U.O.S. di Sassari, National Research Council of Italy, Sassari, Italy

    Maria Pina Concas, Simona Vaccargiu & Mario Pirastu

  71. Psychology, University of Illinois, Champaign, IL, USA

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  72. Institute for Computing and Information Sciences, Radboud University Nijmegen, Nijmegen, The Netherlands

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  73. Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy

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  74. Department of Public Health, University of Helsinki, Helsinki, Finland

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  75. Department of Cardiovascular Sciences, University of Leicester, Leicester, UK

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  76. Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK

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  79. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK

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  80. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

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  85. Quantitative Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

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    Massimo Mangino & Cristina Venturini

  89. Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Peter J. van der Most, Behrooz Z. Alizadeh, Jennifer A. Smith & Judith M. Vonk

  90. Public Health Stream, Hunter Medical Research Institute, New Lambton, New South Wales, Australia

    Christopher Oldmeadow, Elizabeth G. Holliday & John R. Attia

  91. Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia

    Christopher Oldmeadow, Elizabeth G. Holliday, Rodney J. Scott & John R. Attia

  92. Centre for Integrated Genomic Medical Research, Institute of Population Health, The University of Manchester, Manchester, UK

    Antony Payton & William E. R. Ollier

  93. School of Psychological Sciences, The University of Manchester, Manchester, UK

    Antony Payton

  94. Department of Health, THL-National Institute for Health and Welfare, Helsinki, Finland

    Natalia Pervjakova, Niina Eklund, Seppo Koskinen, Tomi Mäki-Opas, Veikko Salomaa, Jaakko Kaprio & Markus Perola

  95. Psychiatry, VU University Medical Center and GGZ inGeest, Amsterdam, The Netherlands

    Wouter J. Peyrot, Yusplitri Milaneschi & Brenda W. J. H. Penninx

  96. Laboratory of Genetics, National Institute on Aging, Baltimore, MD, USA

    Yong Qian, Jun Ding & David Schlessinger

  97. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland

    Olli Raitakari

  98. Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland

    Rico Rueedi & Zoltan Kutalik

  99. Swiss Institute of Bioinformatics, Lausanne, Switzerland

    Rico Rueedi & Zoltan Kutalik

  100. Department Of Health Sciences, University of Milan, Milan, Italy

    Erika Salvi & Daniele Cusi

  101. Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Essen, Germany

    Börge Schmidt, Lewin Eisele & Karl-Heinz Jöckel

  102. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA

    Jianxin Shi

  103. Faculty of Medicine, University of Iceland, Reykjavík, Iceland

    Albert V. Smith, Vilmundur Gudnason, Kari Stefansson & Unnur Thorsteinsdottir

  104. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK

    Beate St Pourcain, David M. Evans, George McMahon, Lavinia Paternoster, Susan M. Ring, Thorkild I. A. Sørensen, Nicholas J. Timpson & George Davey Smith

  105. School of Oral and Dental Sciences, University of Bristol, Bristol, UK

    Beate St Pourcain

  106. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany

    Alexander Teumer, Sebastian E. Baumeister, Henry Völzke & Wolfgang Hoffmann

  107. Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Niek Verweij, Klaus Berger & Pim van der Harst

  108. Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany

    Juergen Wellmann

  109. Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Harm-Jan Westra

  110. Partners Center for Personalized Genetic Medicine, Boston, MA, USA

    Harm-Jan Westra

  111. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Harm-Jan Westra, Philip L. de Jager & Aarno Palotie

  112. Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA

    Jingyun Yang, Patricia A. Boyle & David A. Bennett

  113. Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA

    Jingyun Yang & David A. Bennett

  114. Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA

    Wei Zhao, Erin B. Ware & Sharon L. R. Kardia

  115. Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Behrooz Z. Alizadeh

  116. Institute of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany

    Sebastian E. Baumeister

  117. Institute of Molecular Genetics, National Research Council of Italy, Pavia, Italy

    Ginevra Biino

  118. Department of Behavioral Sciences, Rush University Medical Center, Chicago, IL, USA

    Patricia A. Boyle

  119. Warwick Medical School, University of Warwick, Coventry, UK

    Francesco P. Cappuccio

  120. Department of Psychology, University of Edinburgh, Edinburgh, UK

    Gail Davies, David C. M. Liewald & Ian J. Deary

  121. Saïd Business School, University of Oxford, Oxford, UK

    Jan-Emmanuel De Neve

  122. William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK

    Panos Deloukas & Stavroula Kanoni

  123. Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia

    Panos Deloukas

  124. The Berlin Aging Study II; Research Group on Geriatrics, Charité-Universitätsmedizin Berlin, Berlin, Germany

    Ilja Demuth & Elisabeth Steinhagen-Thiessen

  125. Institute of Medical and Human Genetics, Charité-Universitätsmedizin Berlin, Berlin, Germany

    Ilja Demuth

  126. German Socio-Economic Panel Study, DIW Berlin, Berlin, Germany

    Peter Eibich & Martin Kroh

  127. Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, UK

    Peter Eibich

  128. The University of Queensland Diamantina Institute, The Translational Research Institute, Brisbane, Queensland, Australia

    David M. Evans

  129. Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA

    Jessica D. Faul & David R. Weir

  130. Department of Genetics, Division of Statistical Genomics, Washington University School of Medicine, St Louis, MO, USA

    Mary F. Feitosa, Aldi T. Kraja, Ingrid B. Borecki & Michael A. Province

  131. Institute of Human Genetics, University of Bonn, Bonn, Germany

    Andreas J. Forstner

  132. Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany

    Andreas J. Forstner

  133. Institute of Biomedical and Neural Engineering, School of Science and Engineering, Reykjavík University, Reykjavík, Iceland

    Bjarni V. Halldórsson

  134. Laboratory of Epidemiology, Demography, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA

    Tamara B. Harris

  135. Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA

    Andrew C. Heath & Pamela A. Madden

  136. Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK

    Lynne J. Hocking

  137. Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany

    Georg Homuth & Uwe Völker

  138. Manchester Medical School, The University of Manchester, Manchester, UK

    Michael A. Horan

  139. Program in Translational NeuroPsychiatric Genomics, Departments of Neurology and Psychiatry, Brigham and Women’s Hospital, Boston, MA, USA

    Philip L. de Jager

  140. Harvard Medical School, Boston, MA, USA

    Philip L. de Jager

  141. Department of Genes and Environment, Norwegian Institute of Public Health, Oslo, Norway

    Astanand Jugessur, Ronny Myhre & Bo Jacobsson

  142. Department of Genomics of Common Disease, Imperial College London, London, UK

    Marika A. Kaakinen

  143. Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland

    Mika Kähönen

  144. Department of Clinical Physiology, University of Tampere, School of Medicine, Tampere, Finland

    Mika Kähönen

  145. Public Health, Medical School, University of Split, Split, Croatia

    Ivana Kolcic

  146. Institute of Social and Preventive Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland

    Zoltan Kutalik

  147. Neuroepidemiology Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA

    Lenore J. Launer

  148. Amsterdam Brain and Cognition Center, University of Amsterdam, Amsterdam, The Netherlands

    Maël P. Lebreton

  149. Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA

    Douglas F. Levinson

  150. Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

    Peter Lichtner & Thomas Meitinger

  151. Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK

    Riccardo E. Marioni

  152. Department of Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland

    Pedro Marques-Vidal & Peter Vollenweider

  153. Tema BV, Hoofddorp, The Netherlands

    Gerardus A. Meddens

  154. Molecular Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

    Grant W. Montgomery & Dale R. Nyholt

  155. NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK

    Christopher P. Nelson & Nilesh J. Samani

  156. Institute of Health and Biomedical Innovation, Queensland Institute of Technology, Brisbane, Queensland, Australia

    Dale R. Nyholt

  157. Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA

    Aarno Palotie

  158. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland

    Aarno Palotie, Antti-Pekka Sarin & Jaakko Kaprio

  159. Department of Neurology, Massachusetts General Hospital, Boston, MA, USA

    Aarno Palotie

  160. Medical Genetics, Institute for Maternal and Child Health IRCCS “Burlo Garofolo”, Trieste, Italy

    Antonietta Robino, Sheila Ulivi, Diego Vozzi & Paolo Gasparini

  161. Social Impact, Arlington, VA, USA

    Olga Rostapshova

  162. Department of Economics, University of Minnesota Twin Cities, Minneapolis, MN, USA

    Aldo Rustichini

  163. Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem, Evanston, IL, USA

    Alan R. Sanders & Pablo V. Gejman

  164. Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA

    Alan R. Sanders & Pablo V. Gejman

  165. Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland

    Antti-Pekka Sarin

  166. Research Unit for Genetic Epidemiology, Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, General Hospital and Medical University, Graz, Graz, Austria

    Helena Schmidt

  167. Information Based Medicine Stream, Hunter Medical Research Institute, New Lambton, New South Wales, Australia

    Rodney J. Scott

  168. Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Science, University of Leuven, Leuven, Belgium

    Jan A. Staessen

  169. R&D VitaK Group, Maastricht University, Maastricht, The Netherlands

    Jan A. Staessen

  170. Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

    Konstantin Strauch

  171. Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig Maximilians-Universität, Munich, Germany

    Konstantin Strauch

  172. Department of Geriatrics, Florida State University College of Medicine, Tallahassee, FL, USA

    Antonio Terracciano

  173. Department of Health Sciences and Genetics, University of Leicester, Leicester, UK

    Martin D. Tobin

  174. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

    Frank J. A. van Rooij

  175. Research Center for Group Dynamics, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA

    Erin B. Ware

  176. Platform for Genome Analytics, Institutes of Neurogenetics and Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany

    Lars Bertram

  177. Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, Imperial College London, London, UK

    Lars Bertram

  178. Department of Health Sciences, Community and Occupational Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Ute Bültmann

  179. Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari, Italy

    Francesco Cucca

  180. Institute of Biomedical Technologies, Italian National Research Council, Segrate, Milan, Italy

    Daniele Cusi

  181. Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland

    Johan G. Eriksson

  182. Departments of Human Genetics and Psychiatry, Donders Centre for Neuroscience, Nijmegen, The Netherlands

    Barbara Franke

  183. Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Lude Franke & Pim van der Harst

  184. Sidra, Experimental Genetics Division, Sidra, Doha, Qatar

    Paolo Gasparini

  185. Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany

    Hans-Jörgen Grabe

  186. Department of Psychiatry and Psychotherapy, HELIOS-Hospital Stralsund, Stralsund, Germany

    Hans-Jörgen Grabe

  187. Econometric Institute, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, The Netherlands

    Patrick J. F. Groenen

  188. Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands

    Pim van der Harst

  189. Centre for Population Health Research, School of Health Sciences and Sansom Institute, University of South Australia, Adelaide, South Australia, Australia

    Elina Hyppönen

  190. South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia

    Elina Hyppönen & Christine Power

  191. Population, Policy and Practice, UCL Institute of Child Health, University College London, London, UK

    Elina Hyppönen

  192. Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK

    Marjo-Riitta Järvelin

  193. Center for Life Course Epidemiology, Faculty of Medicine, University of Oulu, Oulu, Finland

    Marjo-Riitta Järvelin

  194. Unit of Primary Care, Oulu University Hospital, Oulu, Finland

    Marjo-Riitta Järvelin

  195. Biocenter Oulu, University of Oulu, Oulu, Finland

    Marjo-Riitta Järvelin

  196. Fimlab Laboratories, Tampere, Finland

    Terho Lehtimäki

  197. Department of Clinical Chemistry, University of Tampere, School of Medicine, Tampere, Finland

    Terho Lehtimäki

  198. Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

    Nicholas G. Martin

  199. Centre for Clinical and Cognitive Neuroscience, Institute Brain Behaviour and Mental Health, Salford Royal Hospital, Manchester, UK

    Neil Pendleton

  200. Manchester Institute Collaborative Research in Ageing, University of Manchester, Manchester, UK

    Neil Pendleton

  201. Faculty of Medicine, University of Split, Split, Croatia

    Ozren Polasek

  202. Department of Clinical Genetics, VU Medical Centre, Amsterdam, The Netherlands

    Danielle Posthuma

  203. Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Frederiksberg, Denmark

    Thorkild I. A. Sørensen

  204. Montpellier Business School, Montpellier, France

    A. Roy Thurik

  205. Panteia, Zoetermeer, The Netherlands

    A. Roy Thurik

  206. Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands

    Henning Tiemeier

  207. Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands

    Henning Tiemeier

  208. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

    André G. Uitterlinden

Authors
  1. James J. Lee
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Consortia

23andMe Research Team

  • Michelle Agee
  • , Babak Alipanahi
  • , Adam Auton
  • , Robert K. Bell
  • , Katarzyna Bryc
  • , Sarah L. Elson
  • , Pierre Fontanillas
  • , David A. Hinds
  • , Jennifer C. McCreight.
  • , Karen E. Huber
  • , Nadia K. Litterman
  • , Matthew H. McIntyre
  • , Joanna L. Mountain
  • , Elizabeth S. Noblin
  • , Carrie A. M. Northover
  • , Steven J. Pitts
  • , J. Fah Sathirapongsasuti
  • , Olga V. Sazonova
  • , Janie F. Shelton
  • , Suyash Shringarpure
  • , Chao Tian
  • , Vladimir Vacic
  •  & Catherine H. Wilson

COGENT (Cognitive Genomics Consortium)

Social Science Genetic Association Consortium

  • Aysu Okbay
  • , Jonathan P. Beauchamp
  • , Mark Alan Fontana
  • , James J. Lee
  • , Tune H. Pers
  • , Cornelius A. Rietveld
  • , Patrick Turley
  • , Guo-Bo Chen
  • , Valur Emilsson
  • , S. Fleur W. Meddens
  • , Sven Oskarsson
  • , Joseph K. Pickrell
  • , Kevin Thom
  • , Pascal Timshel
  • , Ronald de Vlaming
  • , Abdel Abdellaoui
  • , Tarunveer S. Ahluwalia
  • , Jonas Bacelis
  • , Clemens Baumbach
  • , Gyda Bjornsdottir
  • , Johannes H. Brandsma
  • , Maria Pina Concas
  • , Jaime Derringer
  • , Nicholas A. Furlotte
  • , Tessel E. Galesloot
  • , Giorgia Girotto
  • , Richa Gupta
  • , Leanne M. Hall
  • , Sarah E. Harris
  • , Edith Hofer
  • , Momoko Horikoshi
  • , Jennifer E. Huffman
  • , Kadri Kaasik
  • , Ioanna P. Kalafati
  • , Robert Karlsson
  • , Augustine Kong
  • , Jari Lahti
  • , Sven J. van der Lee
  • , Christiaan de Leeuw
  • , Penelope A. Lind
  • , Karl-Oskar Lindgren
  • , Tian Liu
  • , Massimo Mangino
  • , Jonathan Marten
  • , Evelin Mihailov
  • , Michael B. Miller
  • , Peter J. van der Most
  • , Christopher Oldmeadow
  • , Antony Payton
  • , Natalia Pervjakova
  • , Wouter J. Peyrot
  • , Yong Qian
  • , Olli Raitakari
  • , Rico Rueedi
  • , Erika Salvi
  • , Börge Schmidt
  • , Katharina E. Schraut
  • , Jianxin Shi
  • , Albert V. Smith
  • , Raymond A. Poot
  • , Beate St Pourcain
  • , Alexander Teumer
  • , Gudmar Thorleifsson
  • , Niek Verweij
  • , Dragana Vuckovic
  • , Juergen Wellmann
  • , Harm-Jan Westra
  • , Jingyun Yang
  • , Wei Zhao
  • , Zhihong Zhu
  • , Behrooz Z. Alizadeh
  • , Najaf Amin
  • , Andrew Bakshi
  • , Sebastian E. Baumeister
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  • , Brenda W. J. H. Penninx
  • , Markus Perola
  • , Nicola Pirastu
  • , Mario Pirastu
  • , Ozren Polasek
  • , Danielle Posthuma
  • , Christine Power
  • , Michael A. Province
  • , Nilesh J. Samani
  • , David Schlessinger
  • , Reinhold Schmidt
  • , Thorkild I. A. Sørensen
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  • , Kari Stefansson
  • , Unnur Thorsteinsdottir
  • , A. Roy Thurik
  • , Nicholas J. Timpson
  • , Henning Tiemeier
  • , Joyce Y. Tung
  • , André G. Uitterlinden
  • , Veronique Vitart
  • , Peter Vollenweider
  • , David R. Weir
  • , James F. Wilson
  • , Alan F. Wright
  • , Dalton C. Conley
  • , Robert F. Krueger
  • , George Davey Smith
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  • , David I. Laibson
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  • , David Cesarini
  •  & Daniel J. Benjamin

Contributions

D.J.B., D.C., P.T. and P.M.V. designed and oversaw the study. A.O. was the lead analyst of the study, responsible for quality control and meta-analyses. Analysts who assisted A.O. in major ways include: E.K. (quality control), O.M. (COJO, MTAG, quality control), T.A.N.-V. (figure preparation), H.L. (quality control), C.L. (quality control), J.S. (UKB association analyses) and R.K.L. (UKB association analyses). P.B. and E.K. conducted the within-family association analyses. The cross-cohort heritability and genetic-correlation analyses were conducted by R.W. and M.Z. The analyses of the X chromosome in UK Biobank were conducted by J.S.; A.O. ran the meta-analysis. J.J.L. organized and oversaw the bioinformatic analyses, with assistance from T.E., E.K., K.T., T.H.P. and P.N.T. Polygenic-prediction analyses were designed and conducted by A.O., K.T. and R.W. Besides the contributions explicitly listed above, T.K., R.L. and R.R. conducted additional analyses for several subsections. C.W. helped with the coordination of the participating cohorts. J.P.B., D.C.C., T.E., M.J., J.J.L., P.D.K., D.I.L., S.F.L., S.O., M.R.R., K.T. and J.Y. provided helpful advice and feedback on various aspects of the study design. All authors contributed to and critically reviewed the manuscript. E.K., J.J.L. and R.W. made especially large contributions to the writing and editing.

Corresponding authors

Correspondence to Aysu Okbay, Peter M. Visscher or Daniel J. Benjamin.

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Competing interests

Anil Malhotra is a consultant for Genomind Inc., Informed DNA, Concert Pharmaceuticals, and Biogen. Nicholas A. Furlotte, Aaron Kleinman and Joyce Tung are employees of 23andMe, Inc.

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Supplementary information

Supplementary Text and Figures

Supplementary Note and Supplementary Figures 1–29

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Supplementary Tables

Supplementary Tables 1–44

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Lee, J.J., Wedow, R., Okbay, A. et al. Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals. Nat Genet 50, 1112–1121 (2018). https://doi.org/10.1038/s41588-018-0147-3

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