GWAS of 126,559 Individuals Identifies Genetic Variants Associated with Educational Attainment
- Cornelius A. Rietveld1,2,
- Sarah E. Medland3,
- Jaime Derringer4,
- Jian Yang5,
- Tõnu Esko6,
- Nicolas W. Martin3,7,
- Harm-Jan Westra8,
- Konstantin Shakhbazov5,9,
- Abdel Abdellaoui10,
- Arpana Agrawal11,
- Eva Albrecht12,
- Behrooz Z. Alizadeh13,
- Najaf Amin14,
- John Barnard15,
- Sebastian E. Baumeister16,
- Kelly S. Benke17,
- Lawrence F. Bielak18,
- Jeffrey A. Boatman19,
- Patricia A. Boyle20,
- Gail Davies21,
- Christiaan de Leeuw22,
- Niina Eklund24,25,
- Daniel S. Evans26,
- Rudolf Ferhmann8,
- Krista Fischer6,
- Christian Gieger12,
- Håkon K. Gjessing27,
- Sara Hägg28,29,30,
- Jennifer R. Harris27,
- Caroline Hayward31,
- Christina Holzapfel32,33,
- Carla A. Ibrahim-Verbaas14,34,
- Erik Ingelsson28,29,30,
- Bo Jacobsson27,35,
- Peter K. Joshi36,
- Astanand Jugessur27,
- Marika Kaakinen37,38,
- Stavroula Kanoni39,
- Juha Karjalainen8,
- Ivana Kolcic40,
- Kati Kristiansson24,25,
- Zoltán Kutalik41,42,
- Jari Lahti43,
- Sang H. Lee3,
- Peng Lin11,
- Penelope A. Lind3,
- Yongmei Liu44,
- Kurt Lohman45,
- Marisa Loitfelder46,
- George McMahon47,
- Pedro Marques Vidal48,
- Osorio Meirelles49,
- Lili Milani6,
- Ronny Myhre27,
- Marja-Liisa Nuotio24,25,
- Christopher J. Oldmeadow50,
- Katja E. Petrovic51,
- Wouter J. Peyrot52,
- Ozren Polašek40,
- Lydia Quaye53,
- Eva Reinmaa6,
- John P. Rice11,
- Thais S. Rizzi22,
- Helena Schmidt54,
- Reinhold Schmidt46,
- Albert V. Smith55,56,
- Jennifer A. Smith18,
- Toshiko Tanaka49,
- Antonio Terracciano49,57,
- Matthijs J. H. M. van der Loos1,2,
- Veronique Vitart31,
- Henry Völzke16,
- Jürgen Wellmann58,
- Lei Yu20,
- Wei Zhao18,
- Jüri Allik59,
- John R. Attia50,
- Stefania Bandinelli60,
- François Bastardot61,
- Jonathan Beauchamp62,
- David A. Bennett20,
- Klaus Berger58,
- Laura J. Bierut11,
- Dorret I. Boomsma10,
- Ute Bültmann63,
- Harry Campbell36,
- Christopher F. Chabris64,
- Lynn Cherkas53,
- Mina K. Chung15,
- Francesco Cucca65,66,
- Mariza de Andrade67,
- Philip L. De Jager68,
- Jan-Emmanuel De Neve69,70,
- Ian J. Deary21,71,
- George V. Dedoussis72,
- Panos Deloukas39,
- Maria Dimitriou72,
- Guðný Eiríksdóttir55,
- Martin F. Elderson73,
- Johan G. Eriksson74,75,76,77,
- David M. Evans78,
- Jessica D. Faul79,
- Luigi Ferrucci49,
- Melissa E. Garcia49,
- Henrik Grönberg30,
- Vilmundur Guðnason55,56,
- Per Hall30,
- Juliette M. Harris53,
- Tamara B. Harris49,
- Nicholas D. Hastie31,
- Andrew C. Heath80,
- Dena G. Hernandez49,
- Wolfgang Hoffmann16,
- Adriaan Hofman81,
- Rolf Holle83,
- Elizabeth G. Holliday50,
- Jouke-Jan Hottenga10,
- William G. Iacono82,
- Thomas Illig33,84,
- Marjo-Riitta Järvelin37,38,85,86,87,
- Mika Kähönen88,
- Jaakko Kaprio24,89,90,
- Robert M. Kirkpatrick82,
- Matthew Kowgier91,
- Antti Latvala89,90,
- Lenore J. Launer49,
- Debbie A. Lawlor78,
- Terho Lehtimäki92,
- Jingmei Li93,
- Paul Lichtenstein30,
- Peter Lichtner94,
- David C. Liewald21,
- Pamela A. Madden11,
- Patrik K. E. Magnusson30,
- Tomi E. Mäkinen95,
- Marco Masala65,
- Matt McGue82,
- Andres Metspalu6,
- Andreas Mielck83,
- Michael B. Miller82,
- Grant W. Montgomery3,
- Sutapa Mukherjee96,97,98,
- Dale R. Nyholt3,
- Ben A. Oostra14,
- Lyle J. Palmer91,
- Aarno Palotie24,39,99,
- Brenda W. J. H. Penninx52,
- Markus Perola24,25,6,
- Patricia A. Peyser18,
- Martin Preisig61,
- Katri Räikkönen43,
- Olli T. Raitakari100,101,
- Anu Realo59,
- Susan M. Ring47,
- Samuli Ripatti24,25,39,
- Fernando Rivadeneira2,102,
- Igor Rudan36,
- Aldo Rustichini103,
- Veikko Salomaa104,
- Antti-Pekka Sarin24,
- David Schlessinger49,
- Rodney J. Scott50,
- Harold Snieder13,
- Beate St Pourcain78,105,
- John M. Starr21,106,
- Jae Hoon Sul107,
- Ida Surakka24,25,
- Rauli Svento108,
- Alexander Teumer109,
- The LifeLines Cohort Study73,
- Henning Tiemeier2,110,
- Frank J. A. van Rooij2,
- David R. Van Wagoner15,
- Erkki Vartiainen111,
- Jorma Viikari112,
- Peter Vollenweider61,
- Judith M. Vonk13,
- Gérard Waeber61,
- David R. Weir79,
- H.-Erich Wichmann113,114,115,
- Elisabeth Widen24,
- Gonneke Willemsen10,
- James F. Wilson36,
- Alan F. Wright31,
- Dalton Conley116,
- George Davey-Smith78,
- Lude Franke8,
- Patrick J. F. Groenen121,
- Albert Hofman2,
- Magnus Johannesson122,
- Sharon L. R. Kardia18,
- Robert F. Krueger82,
- David Laibson117,
- Nicholas G. Martin3,
- Michelle N. Meyer118,119,
- Danielle Posthuma22,110,120,
- A. Roy Thurik1,123,124,
- Nicholas J. Timpson78,
- André G. Uitterlinden2,102,
- Cornelia M. van Duijn14,125,
- Peter M. Visscher3,5,9,*,†,
- Daniel J. Benjamin126,*,†,
- David Cesarini127,128,129,*,†,
- Philipp D. Koellinger1,2,*,†
- 1Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, 3000 DR Rotterdam, Netherlands.
- 2Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, Netherlands.
- 3Queensland Institute of Medical Research, 300 Herston Road, Brisbane, Queensland 4006, Australia.
- 4Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO 80309–0447, USA.
- 5University of Queensland Diamantina Institute, The University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia.
- 6Estonian Genome Center, University of Tartu, Tartu 51010, Estonia.
- 7School of Psychology, University of Queensland, Brisbane, Queensland 4072, Australia.
- 8Department of Genetics, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, Netherlands.
- 9Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
- 10Department of Biological Psychology, VU University Amsterdam, 1081 BT Amsterdam, Netherlands.
- 11Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA.
- 12Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
- 13Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, Netherlands.
- 14Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, Rotterdam 3000 CA, Netherlands.
- 15Heart and Vascular and Lerner Research Institutes, Cleveland Clinic, Cleveland, OH 44195, USA.
- 16Institute for Community Medicine, University Medicine Greifswald, Greifswald 17489, Germany.
- 17Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario M5G 1X5, Canada.
- 18Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109–2029, USA.
- 19Division of Biostatistics, University of Minnesota, Minneapolis, MN 55455, USA.
- 20Rush University Medical Center, Rush Alzheimer’s Disease Center, Chicago, IL 60612, USA.
- 21Centre for Cognitive Aging and Cognitive Epidemiology, The University of Edinburgh, Edinburgh EH8 9JZ, UK.
- 22Department of Functional Genomics, VU University Amsterdam and VU Medical Center, 1081 HV Amsterdam, Netherlands.
- 23Machine Learning Group, Intelligent Systems, Institute for Computing and Information Sciences, Faculty of Science, Radboud University Nijmegen, 6500 GL Nijmegen, Netherlands.
- 24Institute for Molecular Medicine Finland, University of Helsinki, Helsinki 00014, Finland.
- 25Public Health Genomics Unit, Department of Chronic Disease Prevention, The National Institute for Health and Welfare, Helsinki 00014, Finland.
- 26California Pacific Medical Center Research Institute, San Francisco, CA 94107–1728, USA.
- 27Department of Genes and Environment, Division of Epidemiology, Norwegian Institute of Public Health, Nydalen, N-0403 Oslo, Norway.
- 28Department of Medical Sciences, Molecular Epidemiology, Uppsala University, 751 85 Uppsala, Sweden.
- 29Science for Life Laboratory, Uppsala University, 751 23 Uppsala, Sweden.
- 30Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden.
- 31Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
- 32Else Kroener-Fresenius-Centre for Nutritional Medicine, Technische Universität München, University Hospital “Klinikum rechts der Isar,” 81675 Munich, Germany.
- 33Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
- 34Department of Neurology, Erasmus Medical Center, Rotterdam 3000 CA, Netherlands.
- 35Department of Obstetrics and Gynecology, Institute of Public Health, Sahlgrenska Academy, Sahgrenska University Hospital, Gothenburg, 413 45, Sweden.
- 36Centre for Population Health Sciences, The University of Edinburgh, Edinburgh EH8 9AG, UK.
- 37Institute of Health Sciences, University of Oulu, Oulu 90014, Finland.
- 38Biocenter Oulu, University of Oulu, Oulu 90014, Finland.
- 39Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.
- 40Faculty of Medicine, University of Split, 21000 Split, Croatia.
- 41Department of Medical Genetics, University of Lausanne, 1005 Lausanne, Switzerland.
- 42Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
- 43Institute of Behavioral Sciences, University of Helsinki, Helsinki 00014, Finland.
- 44Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University Health Sciences, Winston-Salem, NC 27157–1063, USA.
- 45Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University Health Sciences, Winston-Salem, NC 27157–1063, USA.
- 46Division for Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz 8036, Austria.
- 47School of Social and Community Medicine, University of Bristol, Bristol BS8 2PR, UK.
- 48Institute of Social and Preventive Medicine, Lausanne University Hospital, 1005 Lausanne, Switzerland.
- 49National Institute on Aging, National Institutes of Health, Baltimore, MD 20892, USA.
- 50Hunter Medical Research Institute and Faculty of Health, University of Newcastle, Newcastle, NSW 2308, Australia.
- 51Division of General Neurology, Department of Neurology, General Hospital and Medical University of Graz, Graz 8036, Austria.
- 52Department of Psychiatry, VU University Medical Center, 1081 HL Amsterdam, Netherlands.
- 53Department of Twin Research and Genetic Epidemiology, King’s College London, London SE1 7EH, UK.
- 54Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz 8036, Austria.
- 55Icelandic Heart Association, Kopavogur 201, Iceland.
- 56Department of Medicine, University of Iceland, Reykjavik 101, Iceland.
- 57College of Medicine, Florida State University, Tallahassee, FL 32306–4300, USA.
- 58Institute of Epidemiology and Social Medicine, University of Muenster, 48129 Muenster, Germany.
- 59Department of Psychology, University of Tartu, Tartu 50410, Estonia.
- 60Geriatric Unit, Azienda Sanitaria Firenze, 50125 Florence, Italy.
- 61Department of Internal Medicine, University Hospital, 1011 Lausanne, Switzerland.
- 62Department of Economics, Harvard University, Cambridge, MA 02138, USA.
- 63Department of Health Sciences, Community and Occupational Medicine, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, The Netherlands.
- 64Department of Psychology, Union College, Schenectady, NY 12308, USA.
- 65Istituto di Ricerca Genetica e Biomedica, Consejo de Investigación Nacional Italiano (CNR), Monserrato, 09042, Cagliari, Italy.
- 66Dipartimento di Scienze Biomediche, Università di Sassari, 07100 SS, Italy.
- 67Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN 55905, USA.
- 68Program in Translational Neuropsychiatric Genomics, Department of Neurology, Brigham and Women’s Hospital, Boston, MA 02115, USA.
- 69School of Public Policy, University College London, London WC1H 9QU, UK.
- 70Centre for Economic Performance, London School of Economics, London WC2A 2AE, UK.
- 71Department of Psychology, The University of Edinburgh, Edinburgh EH8 9JZ, UK.
- 72Department of Nutrition and Dietetics, Harokopio University of Athens, Athens 17671, Greece.
- 73LifeLines Cohort Study, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, Netherlands.
- 74Department of General Practice and Primary Health Care, University of Helsinki, Helsinki 00014, Finland.
- 75Unit of General Practice, Helsinki University Central Hospital, Helsinki 00280, Finland.
- 76Folkhälsan Research Center, Helsinki 00250, Finland.
- 77Vaasa Central Hospital, Vaasa 65130, Finland.
- 78MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol BS8 2PR, UK.
- 79Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI 48106, USA.
- 80Division of Biology and Biomedical Sciences, Washington University, St. Louis, MO 63110–1093, USA.
- 81Faculty of Behavioral and Social Sciences, University of Groningen, 9747 AD Groningen, Netherlands.
- 82Department of Psychology, University of Minnesota, Minneapolis, MN 55455–0344, USA.
- 83Institute of Health Economics and Health Care Management, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
- 84Hannover Unified Biobank, Hannover Medical School, 30625 Hannover, Germany.
- 85Department of Epidemiology and Biostatistics, MRC-HPA Centre for Environment and Health, Imperial College London, London W2 1PG, UK.
- 86Unit of Primary Care, Oulu University Hospital, Oulu 90220, Finland.
- 87Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu 90101, Finland.
- 88Department of Clinical Physiology, Tampere University Hospital and University of Tampere School of Medicine, Tampere 33520, Finland.
- 89Department of Public Health, University of Helsinki, 00014 Helsinki, Finland.
- 90Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, 00300 Helsinki, Finland.
- 91Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada.
- 92Department of Clinical Chemistry, Fimlab Laboratories, Tampere University Hospital, Tampere 33520, Finland.
- 93Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore.
- 94Institute of Human Genetics, Helmholtz Centre Munich, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
- 95Department of Health, Functional Capacity and Welfare, National Institute for Health and Welfare, Helsinki 00271, Finland.
- 96Western Australia Sleep Disorders Research Institute, Sir Charles Gairdner Hospital, Perth, Western Australia 6009, Australia.
- 97Department of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
- 98Women’s College Research Institute, University of Toronto, Toronto, Ontario M5G 1N8, Canada.
- 99Department of Medical Genetics, University of Helsinki, 00014 Helsinki, Finland.
- 100Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku 20520, Finland.
- 101Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku 20520, Finland.
- 102Department of Internal Medicine, Erasmus Medical Center, Rotterdam 3000 CA, Netherlands.
- 103Department of Economics, University of Minnesota, Minneapolis, MN 55455–0462, USA.
- 104Chronic Disease Epidemiology Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki 00271, Finland.
- 105School of Oral and Dental Sciences, University of Bristol, Bristol BS1 2LY, UK.
- 106Alzheimer Scotland Dementia Research Centre, The University of Edinburgh, Edinburgh EH8 9JZ, UK.
- 107Department of Computer Science, University of California, Los Angeles, CA 90095, USA.
- 108Department of Economics, Oulu Business School, University of Oulu, Oulu 90014, Finland.
- 109Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald, Greifswald 17487, Germany.
- 110Department of Child and Adolescent Psychiatry, Erasmus Medical Center, 3000 CB Rotterdam, Netherlands.
- 111Division of Welfare and Health Promotion, National Institute for Health and Welfare, Helsinki 00271, Finland.
- 112Department of Medicine, Turku University Hospital, Turku 20520, Finland.
- 113Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, 81377 Munich, Germany.
- 114Klinikum Grosshadern, 81377 Munich, Germany.
- 115Institute of Epidemiology I, Helmholtz Zentrum München, German Research Centre for Environmental Health, 85764 Neuherberg, Germany.
- 116Department of Sociology, New York University, New York, NY 10012, USA.
- 117Department of Economics, Harvard University, Cambridge, MA 02138, USA.
- 118Petrie-Flom Center for Health Law Policy, Biotechnology, andBioethics, Harvard Law School, Cambridge, MA 02138, USA.
- 119Nelson A. Rockefeller Institute of Government, State University of New York, Albany, NY 12203–1003, USA.
- 120Department of Clinical Genetics, VU University Medical Centrer, 1081 BT Amsterdam, Netherlands.
- 121Econometric Institute, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam 3000 DR, Netherlands.
- 122Department of Economics, Stockholm School of Economics, Stockholm 113 83, Sweden.
- 123Panteia, Zoetermeer 2701 AA, Netherlands.
- 124GSCM-Montpellier Business School, Montpellier 34185, France.
- 125Centre for Medical Systems Biology, Leiden University Medical Center, 2300 RC Leiden, Netherlands.
- 126Department of Economics, Cornell University, Ithaca, NY 14853, USA.
- 127Center for Experimental Social Science, Department of Economics, New York University, New York, NY 10012, USA.
- 128Division of Social Science, New York University Abu Dhabi, PO Box 129188, Abu Dhabi, UAE.
- 129Research Institute of Industrial Economics, Stockholm 102 15, Sweden.
- ↵†Corresponding author. E-mail: db468{at}cornell.edu (D.J.B.); dac12{at}nyu.edu (D.C.); koellinger{at}ese.eur.nl (P.D.K.); peter.visscher{at}uq.edu.au (P.M.V.)
-
↵* These authors contributed equally to this work.
Genetic College
Many genomic elements in humans are associated with behavior, including educational attainment. In a genome-wide association study including more than 100,000 samples, Rietveld et al. (p. 1467, published online 30 May; see the Perspective by Flint and Munafò) looked for genes related to educational attainment in Caucasians. Small genetic effects at three loci appeared to impact educational attainment.
Abstract
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 R2 ≈ 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.
- Received for publication 22 January 2013.
- Accepted for publication 16 May 2013.