Genome-wide association study identifies 74 loci associated with educational attainment (original) (raw)

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Acknowledgements

This research was carried out under the auspices of the Social Science Genetic Association Consortium (SSGAC). This research has also been conducted using the UK Biobank Resource. This study was supported by funding from the Ragnar Söderberg Foundation (E9/11), 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, and the NIA/NIH through grants P01-AG005842, P01-AG005842-20S2, P30-AG012810, and T32-AG000186-23 to NBER, and R01-AG042568 to USC. We thank S. Cunningham, N. Galla and J. Rashtian for research assistance. A full list of acknowledgments is provided in the Supplementary Information.

Author information

Author notes

1. Aysu Okbay, Jonathan P. Beauchamp, Mark Alan Fontana, James J. Lee, Tune H. Pers, Cornelius A. Rietveld and Patrick Turley: These authors contributed equally to this work.
2. Peter M. Visscher, Tõnu Esko, Philipp D. Koellinger, David Cesarini and Daniel J. Benjamin: These authors jointly supervised this work.
3. LifeLines Cohort Study: A list of participants and affiliations appears in the Supplementary Information.

Authors and Affiliations

1. Department of Applied Economics, Erasmus School of Economics, Erasmus University, Rotterdam, 3062 PA, Rotterdam, The Netherlands
   Aysu Okbay, Cornelius A. Rietveld, Ronald de Vlaming & A. Roy Thurik
2. Department of Epidemiology, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands
   Aysu Okbay, 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
3. Erasmus University Rotterdam Institute for Behavior and Biology, Rotterdam, 3062 PA, The Netherlands
   Aysu Okbay, Cornelius A. Rietveld, S. Fleur W. Meddens, Ronald de Vlaming, A. Roy Thurik & Philipp D. Koellinger
4. Department of Economics, Harvard University, Cambridge, 02138, Massachusetts, USA
   Jonathan P. Beauchamp, Patrick Turley, Olga Rostapshova & David I. Laibson
5. Center for Economic and Social Research, University of Southern California, Los Angeles, 90089-3332, California, USA
   Mark Alan Fontana & Daniel J. Benjamin
6. Department of Psychology, University of Minnesota Twin Cities, Minneapolis, 55455, Minnesota, USA
   James J. Lee, Michael B. Miller, William G. Iacono, Matt McGue & Robert F. Krueger
7. Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children’s Hospital, Boston, 2116, Massachusetts, USA
   Tune H. Pers & Tõnu Esko
8. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, 02142, Massachusetts, USA
   Tune H. Pers, Pascal Timshel, Harm-Jan Westra, Philip L. de Jager, Aarno Palotie & Tõnu Esko
9. The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, 2100, Denmark
   Tune H. Pers, Tarunveer S. Ahluwalia & Thorkild I. A. Sørensen
10. Department of Epidemiology Research, Statens Serum Institut, Copenhagen, 2300, Denmark
    Tune H. Pers
11. Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia
    Guo-Bo Chen, Zhihong Zhu, Andrew Bakshi, Riccardo E. Marioni, Anna A. E. Vinkhuyzen, Jacob Gratten, Jian Yang & Peter M. Visscher
12. Icelandic Heart Association, Kopavogur, 201, Iceland
    Valur Emilsson & Vilmundur Gudnason
13. Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavík, 107, Iceland
    Valur Emilsson
14. Department of Complex Trait Genetics, VU University, Center for Neurogenomics and Cognitive Research, Amsterdam, 1081 HV, The Netherlands
    S. Fleur W. Meddens, Christiaan deLeeuw, Danielle Posthuma & Philipp D. Koellinger
15. Amsterdam Business School, University of Amsterdam, Amsterdam, 1018 TV, The Netherlands
    S. Fleur W. Meddens, Maël P. Lebreton & Philipp D. Koellinger
16. Department of Government, Uppsala University, Uppsala, 751 20, Sweden
    Sven Oskarsson & Karl-Oskar Lindgren
17. New York Genome Center, New York, 10013, New York, USA
    Joseph K. Pickrell
18. Department of Economics, New York University, New York, 10012, New York, USA
    Kevin Thom & David Cesarini
19. Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, 2800, Denmark
    Pascal Timshel
20. Department of Biological Psychology, VU University Amsterdam, Amsterdam, 1081 BT, The Netherlands
    Abdel Abdellaoui, Jouke-Jan Hottenga, Gonneke Willemsen & Dorret I. Boomsma
21. COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, 2820, Denmark
    Tarunveer S. Ahluwalia, Klaus Bønnelykke, Johannes Waage & Hans Bisgaard
22. Steno Diabetes Center, Gentofte, 2820, Denmark
    Tarunveer S. Ahluwalia & Johannes Waage
23. Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, 416 85, Sweden
    Jonas Bacelis & Bo Jacobsson
24. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, 85764, Germany
    Clemens Baumbach & Christian Gieger
25. Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, 85764, Germany
    Clemens Baumbach & Christa Meisinger
26. deCODE Genetics/Amgen Inc., Reykjavik, 101, Iceland
    Gyda Bjornsdottir, Augustine Kong, Gudmar Thorleifsson, Bjarni Gunnarsson, Bjarni V. Halldórsson, Kari Stefansson & Unnur Thorsteinsdottir
27. Department of Cell Biology, Erasmus Medical Center Rotterdam, 3015 CN, The Netherlands
    Johannes H. Brandsma & Raymond A. Poot
28. Istituto di Ricerca Genetica e Biomedica U.O.S. di Sassari, National Research Council of Italy, Sassari, 07100, Italy
    Maria Pina Concas, Simona Vaccargiu & Mario Pirastu
29. Psychology, University of Illinois, Champaign, 61820, Illinois, USA
    Jaime Derringer
30. 23andMe, Inc., Mountain View, California, 94041, USA
    Nicholas A. Furlotte, David A. Hinds & Joyce Y. Tung
31. Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, 6500 HB, The Netherlands
    Tessel E. Galesloot & Lambertus A. L. M. Kiemeney
32. Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, 34100, Italy
    Giorgia Girotto, Dragana Vuckovic, Ilaria Gandin, Paolo Gasparini & Nicola Pirastu
33. Department of Public Health, University of Helsinki, Helsinki, 00014, Finland
    Richa Gupta, Antti Latvala, Anu Loukola & Jaakko Kaprio
34. Department of Cardiovascular Sciences, University of Leicester, Leicester, LE3 9QP, UK
    Leanne M. Hall, Christopher P. Nelson & Nilesh J. Samani
35. NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, LE3 9QP, UK
    Leanne M. Hall, Christopher P. Nelson & Nilesh J. Samani
36. Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK
    Sarah E. Harris, Gail Davies, David C. M. Liewald, Riccardo E. Marioni & Ian J. Deary
37. Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK
    Sarah E. Harris & David J. Porteous
38. Department of Neurology, General Hospital and Medical University Graz, Graz, 8036, Austria
    Edith Hofer, Katja E. Petrovic, Helena Schmidt & Reinhold Schmidt
39. Institute for Medical Informatics, Statistics and Documentation, General Hospital and Medical University Graz, Graz, 8036, Austria
    Edith Hofer
40. Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford, OX3 7LE, UK
    Momoko Horikoshi
41. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK
    Momoko Horikoshi
42. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK
    Jennifer E. Huffman, Jonathan Marten, Caroline Hayward, Veronique Vitart, James F. Wilson & Alan F. Wright
43. Institute of Behavioural Sciences, University of Helsinki, Helsinki, 00014, Finland
    Kadri Kaasik, Jari Lahti, Liisa Keltigangas-Järvinen & Katri Räikkönen
44. Nutrition and Dietetics, Health Science and Education, Harokopio University, Athens, 17671, Greece
    Ioanna P. Kalafati & George V. Dedoussis
45. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, 171 77, Sweden
    Robert Karlsson, Paul Lichtenstein, Nancy L. Pedersen & Patrik K. E. Magnusson
46. Folkhälsan Research Centre, Helsingfors, 00014, Finland
    Jari Lahti, Katri Räikkönen & Johan G. Eriksson
47. Institute for Computing and Information Sciences, Radboud University Nijmegen, Nijmegen, 6525 EC, The Netherlands
    Christiaan deLeeuw
48. Quantitative Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia
    Penelope A. Lind & Sarah E. Medland
49. Lifespan Psychology, Max Planck Institute for Human Development, Berlin, 14195, Germany
    Tian Liu
50. Department of Twin Research and Genetic Epidemiology, King’s College London, London, SE1 7EH, UK
    Massimo Mangino, Lydia Quaye, Cristina Venturini & Tim D. Spector
51. NIHR Biomedical Research Centre, Guy’s and St. Thomas’ Foundation Trust, London, SE1 7EH, UK
    Massimo Mangino & Cristina Venturini
52. Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia
    Evelin Mihailov, Natalia Pervjakova, Reedik Mägi, Lili Milani, Andres Metspalu, Markus Perola & Tõnu Esko
53. Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 9700 RB, The Netherlands
    Peter J. van der Most, Behrooz Z. Alizadeh & Judith M. Vonk
54. Public Health Stream, Hunter Medical Research Institute, New Lambton, NSW 2305, Australia
    Christopher Oldmeadow, Elizabeth G. Holliday & John R. Attia
55. Faculty of Health and Medicine, University of Newcastle, Newcastle, NSW 2300, Australia
    Christopher Oldmeadow, Elizabeth G. Holliday, Rodney J. Scott & John R. Attia
56. Centre for Integrated Genomic Medical Research, Institute of Population Health, The University of Manchester, Manchester, M13 9PT, UK
    Antony Payton & William E. R. Ollier
57. Human Communication and Deafness, School of Psychological Sciences, The University of Manchester, Manchester, M13 9PL, UK
    Antony Payton
58. Department of Health, THL-National Institute for Health and Welfare, Helsinki, 00271, Finland
    Natalia Pervjakova, Niina Eklund, Seppo Koskinen, Tomi Mäki-Opas, Veikko Salomaa, Jaakko Kaprio & Markus Perola
59. Psychiatry, VU University Medical Center & GGZ inGeest, Amsterdam, 1081 HL, The Netherlands
    Wouter J. Peyrot, Yusplitri Milaneschi & Brenda W. J. H. Penninx
60. Laboratory of Genetics, National Institute on Aging, Baltimore, 21224, Maryland, USA
    Yong Qian, Jun Ding & David Schlessinger
61. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, 20521, Finland
    Olli Raitakari
62. Department of Medical Genetics, University of Lausanne, Lausanne, 1005, Switzerland
    Rico Rueedi & Zoltan Kutalik
63. Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland
    Rico Rueedi & Zoltan Kutalik
64. Department Of Health Sciences, University of Milan, Milano, 20142, Italy
    Erika Salvi & Daniele Cusi
65. Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Essen, 45147, Germany
    Börge Schmidt, Lewin Eisele & Karl-Heinz Jöckel
66. Centre for Global Health Research, The Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, UK
    Katharina E. Schraut, Harry Campbell, Peter K. Joshi, Igor Rudan, Ozren Polasek & James F. Wilson
67. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, 20892-9780, Maryland, USA
    Jianxin Shi
68. Icelandic Heart Association, Kopavogur, 201, Iceland
    Albert V. Smith
69. Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland
    Albert V. Smith, Vilmundur Gudnason, Kari Stefansson & Unnur Thorsteinsdottir
70. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, BS8 2BN, UK
    Beate St Pourcain, David M. Evans, George McMahon, Lavinia Paternoster, Susan M. Ring, Thorkild I. A. Sørensen, Nicholas J. Timpson & George Davey Smith
71. School of Oral and Dental Sciences, University of Bristol, Bristol, BS1 2LY, UK
    Beate St Pourcain
72. Institute for Community Medicine, University Medicine Greifswald, Greifswald, 17475, Germany
    Alexander Teumer, Sebastian E. Baumeister, Henry Völzke & Wolfgang Hoffmann
73. Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, 9700 RB, The Netherlands
    Niek Verweij, Klaus Berger & Pim van der Harst
74. Institute of Epidemiology and Social Medicine, University of Münster, Münster, 48149, Germany
    Juergen Wellmann
75. Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, 02115, Massachusetts, USA
    Harm-Jan Westra
76. Partners Center for Personalized Genetic Medicine, Boston, 02115, Massachusetts, USA
    Harm-Jan Westra
77. Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, 60612, Illinois, USA
    Jingyun Yang, Patricia A. Boyle & David A. Bennett
78. Department of Neurological Sciences, Rush University Medical Center, Chicago, 60612, Illinois, USA
    Jingyun Yang & David A. Bennett
79. Department of Epidemiology, University of Michigan, Ann Arbor, 48109, Michigan, USA
    Wei Zhao, Jennifer A. Smith, Erin B. Ware & Sharon L. R. Kardia
80. Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, 9713 GZ, The Netherlands
    Behrooz Z. Alizadeh
81. Institute of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, D-93053, Germany
    Sebastian E. Baumeister
82. Institute of Molecular Genetics, National Research Council of Italy, Pavia, 27100, Italy
    Ginevra Biino
83. Department of Behavioral Sciences, Rush University Medical Center, Chicago, 60612, Illinois, USA
    Patricia A. Boyle
84. Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK
    Francesco P. Cappuccio
85. Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK
    Gail Davies, David C. M. Liewald & Ian J. Deary
86. Saïd Business School, University of Oxford, Oxford, OX1 1HP, UK
    Jan-Emmanuel De Neve
87. William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK
    Panos Deloukas & Stavroula Kanoni
88. Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, 21589, Saudi Arabia
    Panos Deloukas
89. The Berlin Aging Study II; Research Group on Geriatrics, Charité – Universitätsmedizin Berlin, Germany, 13347, Berlin, Germany
    Ilja Demuth & Elisabeth Steinhagen-Thiessen
90. Institute of Medical and Human Genetics, Charité-Universitätsmedizin, Berlin, 13353, Berlin, Germany
    Ilja Demuth
91. German Socio- Economic Panel Study, DIW Berlin, 10117, Berlin, Germany
    Peter Eibich & Martin Kroh
92. Nuffield Department of Population Health, Health Economics Research Centre, University of Oxford, Oxford, OX3 7LF, UK
    Peter Eibich
93. The University of Queensland Diamantina Institute, The Translational Research Institute, Brisbane, QLD 4102, Australia
    David M. Evans, Jian Yang & Peter M. Visscher
94. Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, 48109, Michigan, USA
    Jessica D. Faul & David R. Weir
95. Department of Genetics, Division of Statistical Genomics, Washington University School of Medicine, St. Louis, 63018, Missouri, USA
    Mary F. Feitosa, Aldi T. Kraja, Ingrid B. Borecki & Michael A. Province
96. Institute of Human Genetics, University of Bonn, Bonn, 53127, Germany
    Andreas J. Forstner
97. Department of Genomics, Life and Brain Center, University of Bonn, Bonn, 53127, Germany
    Andreas J. Forstner
98. Institute of Biomedical and Neural Engineering, School of Science and Engineering, Reykjavik University, Reykjavik, 101, Iceland
    Bjarni V. Halldórsson
99. Laboratory of Epidemiology, Demography, National Institute on Aging, National Institutes of Health, Bethesda, 20892-9205, Maryland, USA
    Tamara B. Harris
100. Department of Psychiatry, Washington University School of Medicine, St. Louis, 63110, Missouri, USA
     Andrew C. Heath & Pamela A. Madden
101. Division of Applied Health Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK
     Lynne J. Hocking
102. Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, 17475, Germany
     Georg Homuth & Uwe Völker
103. Manchester Medical School, The University of Manchester, Manchester, M13 9PT, UK
     Michael A. Horan
104. Departments of Neurology & Psychiatry, Program in Translational NeuroPsychiatric Genomics, Brigham and Women’s Hospital, Boston, 02115, Massachusetts, USA
     Philip L. de Jager
105. Harvard Medical School, Boston, 02115, Massachusetts, USA
     Philip L. de Jager
106. Department of Genes and Environment, Norwegian Institute of Public Health, Oslo, N-0403, Norway
     Astanand Jugessur, Ronny Myhre & Bo Jacobsson
107. Department of Genomics of Common Disease, Imperial College London, London, W12 0NN, UK
     Marika A. Kaakinen
108. Department of Clinical Physiology, Tampere University Hospital, Tampere, 33521, Finland
     Mika Kähönen
109. Department of Clinical Physiology, University of Tampere, School of Medicine, Tampere, 33014, Finland
     Mika Kähönen
110. Public Health, Medical School, University of Split, Split, 21000, Croatia
     Ivana Kolcic
111. Institute of Social and Preventive Medicine, Lausanne University Hospital (CHUV), Lausanne, 1010, Switzerland
     Zoltan Kutalik
112. Neuroepidemiology Section, National Institute on Aging, National Institutes of Health, Bethesda, 20892-9205, Maryland, USA
     Lenore J. Launer
113. Amsterdam Brain and Cognition Center, University of Amsterdam, Amsterdam, 1018 XA, The Netherlands
     Maël P. Lebreton
114. Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, 94305-5797, California, USA
     Douglas F. Levinson
115. Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, 85764, Germany
     Peter Lichtner & Thomas Meitinger
116. Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK
     Riccardo E. Marioni
117. Department of Internal Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, 1011, Switzerland
     Pedro Marques-Vidal & Peter Vollenweider
118. Tema BV, Hoofddorp, 2131 HE, The Netherlands
     Gerardus A. Meddens
119. Molecular Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia
     Grant W. Montgomery & Dale R. Nyholt
120. Institute of Health and Biomedical Innovation, Queensland Institute of Technology, Brisbane, QLD 4059, Australia
     Dale R. Nyholt
121. Department of Medicine, Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA
     Aarno Palotie
122. The Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, 02142, Massachusetts, USA
     Aarno Palotie
123. Department of Psychiatry, Psychiatric & Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA
     Aarno Palotie
124. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, 00014, Finland
     Aarno Palotie, Antti-Pekka Sarin & Jaakko Kaprio
125. Department of Neurology, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA
     Aarno Palotie
126. Medical Genetics, Institute for Maternal and Child Health IRCCS “Burlo Garofolo”, Trieste, 34100, Italy
     Antonietta Robino, Sheila Ulivi & Paolo Gasparini
127. Social Impact, Arlington, 22201, Virginia, USA
     Olga Rostapshova & Diego Vozzi
128. Department of Economics, University of Minnesota Twin Cities, Minneapolis, 55455, Minnesota, USA
     Aldo Rustichini
129. Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem, Evanston, 60201-3137, Illinois, USA
     Alan R. Sanders & Pablo V. Gejman
130. Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, 60637, Illinois, USA
     Alan R. Sanders & Pablo V. Gejman
131. Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, 00300, Finland
     Antti-Pekka Sarin
132. Research Unit for Genetic Epidemiology, Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, General Hospital and Medical University, Graz, 8010, Graz, Austria
     Helena Schmidt
133. Information Based Medicine Stream, Hunter Medical Research Institute, New Lambton, 2305, NSW, Australia
     Rodney J. Scott
134. Medical Research Institute, University of Dundee, Dundee, DD1 9SY, UK
     Blair H. Smith
135. Department of Cardiovascular Science, Research Unit Hypertension and Cardiovascular Epidemiology, University of Leuven, Leuven, 3000, Belgium
     Jan A. Staessen
136. R&D VitaK Group, Maastricht University, Maastricht, 6229 EV, The Netherlands
     Jan A. Staessen
137. Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, 85764, Germany
     Konstantin Strauch
138. Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig Maximilians-Universität, Munich, 81377, Germany
     Konstantin Strauch
139. Department of Geriatrics, Florida State University College of Medicine, Tallahassee, 32306, Florida, USA
     Antonio Terracciano
140. Department of Health Sciences and Genetics, University of Leicester, Leicester, LE1 7RH, UK
     Martin D. Tobin
141. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands
     Frank J. A. van Rooij
142. Research Center for Group Dynamics, Institute for Social Research, University of Michigan, Ann Arbor, 48104, Michigan, USA
     Erin B. Ware
143. Platform for Genome Analytics, Institutes of Neurogenetics & Integrative and Experimental Genomics, University of Lübeck, Lübeck, 23562, Germany
     Lars Bertram
144. Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London, SW7 2AZ, UK
     Lars Bertram
145. Department of Health Sciences, Community & Occupational Medicine, University of Groningen, University Medical Center Groningen, Groningen, 9713 AV, The Netherlands
     Ute Bültmann
146. Department of Psychology, Union College, Schenectady, 12308, New York, USA
     Christopher F. Chabris
147. Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, 9042, Cagliari, Italy
     Francesco Cucca
148. Institute of Biomedical Technologies, Italian National Research Council, Segrate (Milano), 20090, Italy
     Daniele Cusi
149. Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, 00014, Finland
     Johan G. Eriksson
150. Departments of Human Genetics and Psychiatry, Donders Centre for Neuroscience, Nijmegen, 6500 HB, The Netherlands
     Barbara Franke
151. Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, 9700 RB, The Netherlands
     Lude Franke & Pim van der Harst
152. Experimental Genetics Division, Sidra, Sidra, 26999, Doha, Qatar
     Paolo Gasparini
153. Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, 17475, Germany
     Hans-Jörgen Grabe
154. Department of Psychiatry and Psychotherapy, HELIOS-Hospital Stralsund, Stralsund, 18437, Germany
     Hans-Jörgen Grabe
155. Econometric Institute, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, 3062 PA, The Netherlands
     Patrick J. F. Groenen
156. Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, 1105 AZ, The Netherlands
     Pim van der Harst
157. Generation Scotland, Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK
     Caroline Hayward
158. Centre for Population Health Research, School of Health Sciences and Sansom Institute, University of South Australia, Adelaide, SA 5000, Australia
     Elina Hyppönen
159. South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia
     Elina Hyppönen
160. Population, Policy and Practice, UCL Institute of Child Health, London, WC1N 1EH, UK
     Elina Hyppönen & Christine Power
161. Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of Public Health, Imperial College London, London, W2 1PG, UK
     Marjo-Riitta Järvelin
162. Center for Life Course Epidemiology, Faculty of Medicine, University of Oulu, Oulu, 90014, Finland
     Marjo-Riitta Järvelin
163. Unit of Primary Care, Oulu University Hospital, Oulu, 90029, Finland
     Marjo-Riitta Järvelin
164. Biocenter Oulu, University of Oulu, Oulu, 90014, Finland
     Marjo-Riitta Järvelin
165. Fimlab Laboratories, Tampere, 33520, Finland
     Terho Lehtimäki
166. Department of Clinical Chemistry, University of Tampere, School of Medicine, Tampere, 33014, Finland
     Terho Lehtimäki
167. Economics, NYU Shanghai, Pudong, 200122, China
     Steven F. Lehrer
168. Policy Studies, Queen’s University, Kingston, Ontario, K7L 3N6, Canada
     Steven F. Lehrer
169. Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia
     Nicholas G. Martin
170. Institute of Molecular and Cell Biology, University of Tartu, Tartu, 51010, Estonia
     Andres Metspalu
171. Centre for Clinical and Cognitive Neuroscience, Institute Brain Behaviour and Mental Health, Salford Royal Hospital, Manchester, M6 8HD, UK
     Neil Pendleton
172. Manchester Institute for Collaborative Research in Ageing, University of Manchester, Manchester, M13 9PL, UK
     Neil Pendleton
173. Faculty of Medicine, University of Split, Split, 21000, Croatia
     Ozren Polasek
174. Department of Clinical Genetics, VU Medical Centre, Amsterdam, 1081 HV, The Netherlands
     Danielle Posthuma
175. Institute of Preventive Medicine. Bispebjerg and Frederiksberg Hospitals, The Capital Region, Frederiksberg, 2000, Denmark
     Thorkild I. A. Sørensen
176. Montpellier Business School, Montpellier, 34080, France
     A. Roy Thurik
177. Panteia, Zoetermeer, 2715 CA, The Netherlands
     A. Roy Thurik
178. Department of Psychiatry, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands
     Henning Tiemeier
179. Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands
     Henning Tiemeier
180. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands
     André G. Uitterlinden
181. Department of Sociology, New York University, New York, 10012, New York, USA
     Dalton C. Conley
182. School of Medicine, New York University, New York, 10016, New York, USA
     Dalton C. Conley
183. Bioethics Program, Union Graduate College – Icahn School of Medicine at Mount Sinai, Schenectady, 12308, New York, USA
     Michelle N. Meyer
184. Department of Economics, Stockholm School of Economics, Stockholm, 113 83, Sweden
     Magnus Johannesson
185. Department of Genetics, Harvard Medical School, Boston, 02115, Massachusetts, USA
     Tõnu Esko
186. Research Institute for Industrial Economics, Stockholm, 10215, Sweden
     David Cesarini

Authors

1. Aysu Okbay
2. Jonathan P. Beauchamp
3. Mark Alan Fontana
4. James J. Lee
5. Tune H. Pers
6. Cornelius A. Rietveld
7. Patrick Turley
8. Guo-Bo Chen
9. Valur Emilsson
10. S. Fleur W. Meddens
11. Joseph K. Pickrell
12. Kevin Thom
13. Pascal Timshel
14. Ronald de Vlaming
15. Abdel Abdellaoui
16. Tarunveer S. Ahluwalia
17. Jonas Bacelis
18. Clemens Baumbach
19. Gyda Bjornsdottir
20. Johannes H. Brandsma
21. Maria Pina Concas
22. Jaime Derringer
23. Nicholas A. Furlotte
24. Tessel E. Galesloot
25. Giorgia Girotto
26. Richa Gupta
27. Leanne M. Hall
28. Sarah E. Harris
29. Edith Hofer
30. Momoko Horikoshi
31. Jennifer E. Huffman
32. Kadri Kaasik
33. Ioanna P. Kalafati
34. Robert Karlsson
35. Augustine Kong
36. Jari Lahti
37. Sven J. van der Lee
38. Christiaan deLeeuw
39. Penelope A. Lind
40. Karl-Oskar Lindgren
41. Tian Liu
42. Massimo Mangino
43. Jonathan Marten
44. Evelin Mihailov
45. Michael B. Miller
46. Peter J. van der Most
47. Christopher Oldmeadow
48. Antony Payton
49. Natalia Pervjakova
50. Wouter J. Peyrot
51. Yong Qian
52. Olli Raitakari
53. Rico Rueedi
54. Erika Salvi
55. Börge Schmidt
56. Katharina E. Schraut
57. Jianxin Shi
58. Albert V. Smith
59. Raymond A. Poot
60. Beate St Pourcain
61. Alexander Teumer
62. Gudmar Thorleifsson
63. Niek Verweij
64. Dragana Vuckovic
65. Juergen Wellmann
66. Harm-Jan Westra
67. Jingyun Yang
68. Wei Zhao
69. Zhihong Zhu
70. Behrooz Z. Alizadeh
71. Najaf Amin
72. Andrew Bakshi
73. Sebastian E. Baumeister
74. Ginevra Biino
75. Klaus Bønnelykke
76. Patricia A. Boyle
77. Harry Campbell
78. Francesco P. Cappuccio
79. Gail Davies
80. Jan-Emmanuel De Neve
81. Panos Deloukas
82. Ilja Demuth
83. Jun Ding
84. Peter Eibich
85. Lewin Eisele
86. Niina Eklund
87. David M. Evans
88. Jessica D. Faul
89. Mary F. Feitosa
90. Andreas J. Forstner
91. Ilaria Gandin
92. Tamara B. Harris
93. Andrew C. Heath
94. Lynne J. Hocking
95. Elizabeth G. Holliday
96. Georg Homuth
97. Michael A. Horan
98. Jouke-Jan Hottenga
99. Philip L. de Jager
100. Peter K. Joshi
101. Astanand Jugessur
102. Marika A. Kaakinen
103. Mika Kähönen
104. Stavroula Kanoni
105. Liisa Keltigangas-Järvinen
106. Lambertus A. L. M. Kiemeney
107. Ivana Kolcic
108. Seppo Koskinen
109. Aldi T. Kraja
110. Martin Kroh
111. Zoltan Kutalik
112. Antti Latvala
113. Lenore J. Launer
114. Maël P. Lebreton
115. Douglas F. Levinson
116. Paul Lichtenstein
117. Peter Lichtner
118. David C. M. Liewald
119. LifeLines Cohort Study
120. Anu Loukola
121. Pamela A. Madden
122. Reedik Mägi
123. Tomi Mäki-Opas
124. Riccardo E. Marioni
125. Pedro Marques-Vidal
126. Gerardus A. Meddens
127. George McMahon
128. Christa Meisinger
129. Thomas Meitinger
130. Yusplitri Milaneschi
131. Lili Milani
132. Grant W. Montgomery
133. Ronny Myhre
134. Christopher P. Nelson
135. Dale R. Nyholt
136. William E. R. Ollier
137. Aarno Palotie
138. Lavinia Paternoster
139. Nancy L. Pedersen
140. Katja E. Petrovic
141. David J. Porteous
142. Katri Räikkönen
143. Susan M. Ring
144. Antonietta Robino
145. Olga Rostapshova
146. Igor Rudan
147. Aldo Rustichini
148. Veikko Salomaa
149. Alan R. Sanders
150. Antti-Pekka Sarin
151. Helena Schmidt
152. Rodney J. Scott
153. Blair H. Smith
154. Jennifer A. Smith
155. Jan A. Staessen
156. Elisabeth Steinhagen-Thiessen
157. Konstantin Strauch
158. Antonio Terracciano
159. Martin D. Tobin
160. Sheila Ulivi
161. Simona Vaccargiu
162. Lydia Quaye
163. Frank J. A. van Rooij
164. Cristina Venturini
165. Anna A. E. Vinkhuyzen
166. Uwe Völker
167. Henry Völzke
168. Judith M. Vonk
169. Diego Vozzi
170. Johannes Waage
171. Erin B. Ware
172. Gonneke Willemsen
173. John R. Attia
174. David A. Bennett
175. Klaus Berger
176. Lars Bertram
177. Hans Bisgaard
178. Dorret I. Boomsma
179. Ingrid B. Borecki
180. Ute Bültmann
181. Christopher F. Chabris
182. Francesco Cucca
183. Daniele Cusi
184. Ian J. Deary
185. George V. Dedoussis
186. Cornelia M. van Duijn
187. Johan G. Eriksson
188. Barbara Franke
189. Lude Franke
190. Paolo Gasparini
191. Pablo V. Gejman
192. Christian Gieger
193. Hans-Jörgen Grabe
194. Jacob Gratten
195. Patrick J. F. Groenen
196. Vilmundur Gudnason
197. Pim van der Harst
198. Caroline Hayward
199. David A. Hinds
200. Wolfgang Hoffmann
201. Elina Hyppönen
202. William G. Iacono
203. Bo Jacobsson
204. Marjo-Riitta Järvelin
205. Karl-Heinz Jöckel
206. Jaakko Kaprio
207. Sharon L. R. Kardia
208. Terho Lehtimäki
209. Steven F. Lehrer
210. Patrik K. E. Magnusson
211. Nicholas G. Martin
212. Matt McGue
213. Andres Metspalu
214. Neil Pendleton
215. Brenda W. J. H. Penninx
216. Markus Perola
217. Nicola Pirastu
218. Mario Pirastu
219. Ozren Polasek
220. Danielle Posthuma
221. Christine Power
222. Michael A. Province
223. Nilesh J. Samani
224. David Schlessinger
225. Reinhold Schmidt
226. Thorkild I. A. Sørensen
227. Tim D. Spector
228. Kari Stefansson
229. Unnur Thorsteinsdottir
230. A. Roy Thurik
231. Nicholas J. Timpson
232. Henning Tiemeier
233. Joyce Y. Tung
234. André G. Uitterlinden
235. Veronique Vitart
236. Peter Vollenweider
237. David R. Weir
238. James F. Wilson
239. Alan F. Wright
240. Dalton C. Conley
241. Robert F. Krueger
242. George Davey Smith
243. Albert Hofman
244. David I. Laibson
245. Sarah E. Medland
246. Michelle N. Meyer
247. Jian Yang
248. Magnus Johannesson
249. Peter M. Visscher
250. Tõnu Esko
251. Philipp D. Koellinger
252. David Cesarini
253. Daniel J. Benjamin

Contributions

Study design and management: D.J.B., D.Ce., T.E., M.J., P.D.K. and P.M.V. Quality control and meta-analysis: A.O., G.B.C., T.E., M.A.F., C.A.R. and T.H.P. Stratification: P.T., J.P.B., C.A.R. and J.Y. Genetic overlap: J.P.B., M.A.F., P.T. Biological annotation: J.J.L., T.E., T.H.P., J.K.P., J.H.B., J.P.B., L.F., V.E., G.A.M., M.A.F., S.F.W.M., P.Ti., R.A.P., R.d.V. and H.J.W. Prediction and mediation: J.P.B., M.A.F. and J.Y. G×E: D.Co., S.F.L., K.O.L., S.O. and K.T. Replication in UKB: M.A.F. and C.A.R. SSGAC advisory board: D.Co., T.E., A.H., R.F.K., D.I.L., S.E.M., M.N.M., G.D.S. and P.M.V. All authors contributed to and critically reviewed the manuscript. Authors not listed above contributed to the recruitment, genotyping, or data processing for the contributing components of the meta-analysis. For a full list of author contributions, see Supplementary Information section 8.

Corresponding authors

Correspondence toPeter M. Visscher, Philipp D. Koellinger, David Cesarini or Daniel J. Benjamin.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Additional information

Results can be downloaded from the SSGAC website (http://ssgac.org/Data.php). Data for our analyses come from many studies and organizations, some of which are subject to a MTA, and are listed in the Supplementary Information.

Extended data figures and tables

Extended Data Figure 1 Q–Q plot of the genome-wide association meta-analysis of 64 EduYears results files (n = 293,723).

Observed and expected P values are on a −log10 scale (two-tailed). The grey region depicts the 95% confidence interval under the null hypothesis of a uniform P value distribution. The observed _λ_GC is 1.28. (As reported in Supplementary Information section 1.5.4, the unweighted mean _λ_GC is 1.02, the unweighted median is 1.01, and the range across cohorts is 0.95–1.15.)

Extended Data Figure 2 The distribution of effect sizes of the 74 lead SNPs.

a, SNPs ordered by absolute value of the standardized effect of one more copy of the education-increasing allele, with 95% confidence intervals. b, SNPs ordered by _R_2. Effects on EduYears are benchmarked against the top 74 genome-wide significant hits identified in the largest GWAS conducted to date of height and body mass index (BMI), and the 48 associations reported for waist-to-hip ratio adjusted for BMI (WHR). These results are based on the GIANT consortium’s publicly available results for pooled analyses restricted to European-ancestry individuals: https://www.broadinstitute.org/collaboration/giant/index.php/GIANT_consortium.

Extended Data Figure 3 Assessing the extent to which population stratification affects the estimates from the GWAS.

a, LD score regression plot with the summary statistics from the GWAS. Each point represents an LD score quantile for a chromosome (the x and y coordinates of the point are the mean LD score and the mean _χ_2 statistic of variants in that quantile). That the intercept is close to 1 and that the _χ_2 statistics increase linearly with the LD scores suggest that the bulk of the inflation in the _χ_2 statistics is due to true polygenic signal and not to population stratification. b, Estimates and 95% confidence intervals from individual-level and within-family regressions of EduYears on polygenic scores, for scores constructed with sets of SNPs meeting different P value thresholds. In addition to the analyses shown here, we conduct a sign concordance test, and we decompose the variance of the polygenic score. Overall, these analyses suggest that population stratification is unlikely to be a major concern for our 74 lead SNPs. See Supplementary Information section 3 for additional details.

Extended Data Figure 4 Replication of 74 lead SNPs in the UK Biobank data.

Estimated effect sizes (in years of schooling) and 95% confidence intervals of the 74 lead SNPs in the meta-analysis sample (n = 293,723) and the UK Biobank replication sample (n = 111,349). The reference allele is the allele associated with higher values of EduYears in the meta-analysis sample. SNPs are in descending order of _R_2 in the meta-analysis sample. Of the 74 lead SNPs, 72 have the anticipated sign in the replication sample, 52 replicate at the 0.05 significance level, and 7 replicate at the 5 × 10−8 significance level.

Extended Data Figure 5 Q–Q plots for the 74 lead EduYears SNPs (or LD proxies) in published GWAS of other phenotypes.

SNPs with concordant effects on both phenotypes are pink, and SNPs with discordant effects are blue. SNPs outside the grey area pass Bonferroni-corrected significance thresholds that correct for the total number of SNPs we tested (P < 0.05/74 = 6.8 × 10−4) and are labelled with their rs numbers. Observed and expected P values are on a −log10 scale. For the sign concordance test: *P < 0.05, **P < 0.01 and ***P < 0.001.

Extended Data Figure 6 Regional association plots for four of the ten prioritized SNPs for mental health, brain anatomy, and anthropometric phenotypes identified using EduYears as a proxy phenotype.

a, Cognitive performance; b, hippocampus; c, intracranial volume; d, neuroticism. The four were selected because very few genome-wide significant SNPs have been previously reported for these traits. Data sources and methods are described in Supplementary Information section 3. The _R_2 values are from the hg19 / 1000 Genomes Nov 2014 EUR references samples. The figures were created with LocusZoom (http://csg.sph.umich.edu/locuszoom/). Mb, megabases.

Extended Data Figure 7 Application of fgwas to EduYears.

See Supplementary Information section 4.2 for further details. a, The results of single-annotation models. ‘Enrichment’ refers to the factor by which the prior odds of association at an LD-defined region must be multiplied if the region bears the given annotation; this factor is estimated using an empirical Bayes method applied to all SNPs in the GWAS meta-analysis regardless of statistical significance. Annotations were derived from ENCODE and a number of other data sources. Plotted are the base 2 logarithms of the enrichments and their 95% confidence intervals. Multiple instances of the same annotation correspond to independent replicates of the same experiment. b, The results of combining multiple annotations and applying model selection and cross-validation. Although the maximum-likelihood estimates are plotted, model selection was performed with penalized likelihood. c, Reweighting of GWAS loci. Each point represents an LD-defined region of the genome, and shown are the regional posterior probabilities of association (PPAs). The x axis gives the PPA calculated from the GWAS summary statistics alone, whereas the y axis gives the PPA upon reweighting on the basis of the annotations in b. The orange points represent genomic regions where the PPA is equivalent to the standard GWAS significance threshold only upon reweighting.

Extended Data Figure 8 Tissue-level biological annotation.

a, The enrichment factor for a given tissue type is the ratio of variance explained by SNPs in that group to the overall fraction of SNPs in that group. To benchmark the estimates for EduYears, we compare the enrichment factors to those obtained when we use the largest GWAS conducted to date on BMI, height, and waist-to-hip ratio adjusted for BMI. The estimates were produced with the LDSC Python software, using the LD scores and functional annotations introduced in ref. 17 and the HapMap3 SNPs with minor allele frequency >0.05. Each of the ten enrichment calculations for a particular cell type is performed independently, while each controlling for the 52 functional annotation categories in the full baseline model. The error bars show the 95% confidence intervals. b, We took measurements of gene expression by the Genotype-Tissue Expression (GTEx) Consortium and determined whether the genes overlapping EduYears-associated loci are significantly overexpressed (relative to genes in random sets of loci matched by gene density) in each of 37 tissue types. These types are grouped in the panel by organ. The dark bars correspond to tissues where there is significant overexpression. The y axis is the significance on a −log10 scale.

Extended Data Figure 9 Gene-level biological annotation.

a, The DEPICT-prioritized genes for EduYears measured in the BrainSpan Developmental Transcriptome data (red curve) are more strongly expressed in the brain prenatally rather than postnatally. The DEPICT-prioritized genes exhibit similar gene expression levels across different brain regions (grey lines). Analyses were based on log2-transformed RNA-seq data. Error bars represent 95% confidence intervals. b, For each phenotype and disorder, we calculated the overlap between the phenotype’s DEPICT-prioritized genes and genes believed to harbour de novo mutations causing the disorder. The bars correspond to odds ratios. c, DEPICT-prioritized genes in EduYears-associated loci exhibit substantial overlap with genes previously reported to harbour sites where mutations increase risk of intellectual disability and autism spectrum disorder (Supplementary Table 4.6.1).

Extended Data Figure 10 The predictive power of a polygenic score (PGS) varies in Sweden by birth cohort.

Five-year rolling regressions of years of education on the PGS (left axis in all four panels), share of individuals not affected by the comprehensive school reform (a, right axis), and average distance to nearest junior high school (b, right axis), nearest high school (c, right axis) and nearest college/university (d, right axis). The shaded area displays the 95% confidence intervals for the PGS effect.

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Okbay, A., Beauchamp, J., Fontana, M. et al. Genome-wide association study identifies 74 loci associated with educational attainment.Nature 533, 539–542 (2016). https://doi.org/10.1038/nature17671

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• Received: 24 June 2015
• Accepted: 16 March 2016
• Published: 11 May 2016
• Issue date: 26 May 2016
• DOI: https://doi.org/10.1038/nature17671