Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals
Aysu Okbay(Vrije Universiteit Amsterdam), Yeda Wu(The University of Queensland), Nancy Wang(National Bureau of Economic Research), Hariharan Jayashankar(National Bureau of Economic Research), Michael Bennett(National Bureau of Economic Research), Seyed Moeen Nehzati(Anderson University - South Carolina), Julia Sidorenko(The University of Queensland), Hyeokmoon Kweon(Vrije Universiteit Amsterdam), Grant Goldman(National Bureau of Economic Research), Tamara Gjorgjieva(National Bureau of Economic Research), Yunxuan Jiang(23andMe (United States)), Barry Hicks(23andMe (United States)), Chao Tian(23andMe (United States)), David A. Hinds(23andMe (United States)), Rafael Ahlskog(Uppsala University), Patrik K. E. Magnusson(Karolinska Institutet), Sven Oskarsson(Uppsala University), Caroline Hayward(Western General Hospital), Archie Campbell(Western General Hospital), David J. Porteous(Western General Hospital), Jeremy Freese(Stanford University), Pamela Herd(Georgetown University), Michelle Agee(23andMe (United States)), Babak Alipanahi(23andMe (United States)), Adam Auton(23andMe (United States)), Robert K. Bell(23andMe (United States)), Katarzyna Bryc(23andMe (United States)), Sarah L. Elson(23andMe (United States)), Pierre Fontanillas(23andMe (United States)), Nicholas A. Furlotte(23andMe (United States)), David A. Hinds(23andMe (United States)), Karen E. Huber(23andMe (United States)), Aaron Kleinman(23andMe (United States)), Nadia K. Litterman(23andMe (United States)), Jennifer C. McCreight(23andMe (United States)), Matthew H. McIntyre(23andMe (United States)), Joanna L. Mountain(23andMe (United States)), Carrie A. M. Northover(23andMe (United States)), Steven J. Pitts(23andMe (United States)), J. Fah Sathirapongsasuti(23andMe (United States)), Olga V. Sazonova(23andMe (United States)), Janie F. Shelton(23andMe (United States)), Suyash Shringarpure(23andMe (United States)), Joyce Y. Tung(23andMe (United States)), Vladimir Vacic(23andMe (United States)), Catherine H. Wilson(23andMe (United States)), Mark Alan Fontana(University of Southern California), Tune H. Pers(Statens Serum Institut), Cornelius A. Rietveld(Erasmus MC), Guo‐Bo Chen(The University of Queensland), Valur Emilsson(University of Iceland), S. Fleur W. Meddens(Vrije Universiteit Amsterdam), Joseph K. Pickrell(New York Genome Center), Kevin Thom(New York University), Pascal Timshel(Statens Serum Institut), Ronald de Vlaming(Erasmus MC), Abdel Abdellaoui(Vrije Universiteit Amsterdam), Tarunveer S. Ahluwalia(University of Copenhagen), Jonas Bačelis, Clemens Baumbach(Helmholtz Zentrum München), Gyða Björnsdóttir(deCODE Genetics (Iceland)), J Brandsma, Maria Pina Concas(Institute of Genetic and Biomedical Research), Jaime Derringer(University of Illinois Urbana-Champaign), Tessel E. Galesloot(Radboud University Nijmegen), Giorgia Girotto(University of Trieste), Richa Gupta(University of Helsinki), Leanne M. Hall(University of Leicester), Sarah E. Harris(University of Edinburgh), Edith Hofer(Medical University of Graz), Momoko Horikoshi(Centre for Human Genetics), Jennifer E. Huffman(Western General Hospital), Kadri Kaasik(University of Helsinki), Ioanna Panagiota Kalafati(Harokopio University of Athens), Robert Karlsson(Karolinska Institutet), Jari Lahti(University of Helsinki), Sven J. van der Lee(Medical University of Graz), Christiaan de Leeuw(Radboud University Nijmegen), Penelope A. Lind(QIMR Berghofer Medical Research Institute), Karl‐Oskar Lindgren(Uppsala University), Tian Liu(Max Planck Institute for Human Development), Massimo Mangino(King's College London), Jonathan Marten(Western General Hospital), Evelin Mihailov(University of Tartu), Michael Miller(University of Minnesota), Peter J. van der Most(University Medical Center Groningen), Christopher Oldmeadow(Hunter Medical Research Institute), Antony Payton(University of Manchester), Natalia Pervjakova(Finnish Institute for Health and Welfare), Wouter J. Peyrot(GGZ inGeest), Yong Qian(National Institute on Aging), Olli T. Raitakari(University of Turku), Rico Rueedi(SIB Swiss Institute of Bioinformatics), Erika Salvi(University of Milan), Börge Schmidt(Institut für Medizinische Informatik, Biometrie und Epidemiologie), Katharina E. Schraut(University of Edinburgh), Jianxin Shi(National Cancer Institute), Albert V. Smith(University of Iceland), Raymond A. Poot, Beaté St Pourcain(University Of Bristol Dental Hospital), Alexander Teumer(Universitätsmedizin Greifswald), Guðmar Þorleifsson(deCODE Genetics (Iceland)), Niek Verweij(University Medical Center Groningen), Dragana Vuckovic(University of Trieste), Juergen Wellmann, Harm-Jan Westra(Broad Institute), Jingyun Yang(Rush University Medical Center), Wei Zhao(University of Michigan), Zhihong Zhu(The University of Queensland), Behrooz Z. Alizadeh(University Medical Center Groningen), Najaf Amin(Erasmus MC), Andrew Bakshi(The University of Queensland), Sebastian E. Baumeister(Universitätsmedizin Greifswald), Ginevra Biino(National Research Council), Klaus Bønnelykke(University of Copenhagen), Patricia A. Boyle(Rush University Medical Center), Harry Campbell(University of Edinburgh), Francesco P. Cappuccio(University of Warwick), Gail Davies(University of Edinburgh), Jan-Emmanuel De Neve(University of Oxford), Panos Deloukas(Queen Mary University of London), Ilja Demuth(Berlin Institute of Health at Charité - Universitätsmedizin Berlin), Jun Ding(National Institute on Aging), Peter Eibich(German Institute for Economic Research), Lewin Eisele(Institut für Medizinische Informatik, Biometrie und Epidemiologie), Niina Eklund(Finnish Institute for Health and Welfare), David M. Evans(Translational Research Institute), Jessica D. Faul(University of Michigan), Mary F. Feitosa(Washington University in St. Louis), Andreas J. Forstner(University of Bonn), Ilaria Gandin(University of Trieste), Bjarni Gunnarsson(deCODE Genetics (Iceland)), Bjarni V. Halldórsson(Reykjavík University), Tamara B. Harris(National Institutes of Health), Andrew C. Heath(Washington University in St. Louis), Lynne J. Hocking(University of Aberdeen), Elizabeth G. Holliday(Hunter Medical Research Institute), Georg Homuth(Universitätsmedizin Greifswald), Michael A. Horan(University of Manchester), Jouke‐Jan Hottenga(Vrije Universiteit Amsterdam), Philip L. De Jager(Broad Institute), Peter K. Joshi(Institute of Social and Preventive Medicine), Astanand Jugessur(Norwegian Institute of Public Health), Marika Kaakinen(Genomics England), Mika Kähönen(Tampere University Hospital), Stavroula Kanoni(Queen Mary University of London), Liisa Keltigangas-Järvinen(University of Helsinki), Lambertus A. Kiemeney(Radboud University Nijmegen), Ivana Kolčić(University of Split), Seppo Koskinen(Finnish Institute for Health and Welfare), Aldi T. Kraja(Washington University in St. Louis), Martin Kroh(German Institute for Economic Research), Zoltán Kutalik(SIB Swiss Institute of Bioinformatics), Antti Latvala(University of Helsinki), Lenore J. Launer(National Institutes of Health), Maël P. Lebreton(University of Amsterdam), Douglas F. Levinson(Stanford University), Paul Lichtenstein(Karolinska Institutet), Peter Lichtner(Helmholtz Zentrum München), David C. Liewald(University of Edinburgh), LifeLines Cohort Study(University of Helsinki), Anu Loukola(University of Helsinki), Pamela A. F. Madden(Washington University in St. Louis), Reedik Mägi(Finnish Institute for Health and Welfare), Tomi Mäki‐Opas(Finnish Institute for Health and Welfare), Riccardo E. Marioni(University of Toronto), Pedro Marques‐Vidal(University of Lausanne), Gerardus A. Meddens(University of Bristol), George McMahon(Helmholtz Zentrum München), Christa Meisinger(Helmholtz Zentrum München), Thomas Meitinger(Helmholtz Zentrum München), Yusplitri Milaneschi(GGZ inGeest), Lili Milani(QIMR Berghofer Medical Research Institute), Grant W. Montgomery(Norwegian Institute of Public Health), Ronny Myhre(Norwegian Institute of Public Health), Christopher P. Nelson(University of Leicester), Dale R. Nyholt(Translational Research Institute), William Ollier(Broad Institute), Aarno Palotie(Broad Institute), Lavinia Paternoster(Karolinska Institutet), Nancy L. Pedersen(Medical University of Graz), Katja Petrovic(Medical University of Graz), Katri Räikkönen(University of Helsinki), Susan M. Ring(IRCCS Materno Infantile Burlo Garofolo), Antonietta Robino(Harvard University), Olga Rostapshova(Harvard University), Igor Rudan(University of Minnesota), Aldo Rustichini(University of Minnesota), Veikko Salomaa(NorthShore University HealthSystem), Alan R. Sanders(University of Helsinki), Antti‐Pekka Sarin(University of Helsinki), Helena Schmidt(Medical University of Graz), Rodney J. Scott(University of Dundee), Blair H. Smith(University Medical Center Groningen), Jennifer A. Smith(University Medical Center Groningen), Jan A. Staessen(Maastricht University), Elisabeth Steinhagen–Thiessen(Zimmer Biomet (Netherlands)), Konstantin Strauch(Florida State University), Antonio Terracciano(Florida State University), Martin D. Tobin(University of Leicester), Sheila Ulivi(IRCCS Materno Infantile Burlo Garofolo), Simona Vaccargiu(King's College London), Lydia Quaye(King's College London), Frank J.A. van Rooij(Guy's and St Thomas' NHS Foundation Trust), Cristina Venturini(The University of Queensland), Anna A. E. Vinkhuyzen(The University of Queensland), Uwe Völker(Universitätsmedizin Greifswald), Henry Völzke(University Medical Center Groningen), Judith M. Vonk(University Medical Center Groningen), Diego Vozzi(Steno Diabetes Centers), Johannes Waage(University of Copenhagen), Erin B. Ware(University of Michigan), Gonneke Willemsen(Hunter Medical Research Institute), John Attia(Rush University Medical Center), David A. Bennett(Rush University Medical Center), Klaus Berger(University Medical Center Groningen), Lars Bertram(University of Copenhagen), Hans Bisgaard(University of Copenhagen), Dorret I. Boomsma(Washington University in St. Louis), Ingrid B. Borecki(University Medical Center Groningen), Ute Bültmann(University Medical Center Groningen), Christopher F. Chabris(Autism & Developmental Medicine Institute), Francesco Cucca(University of Milan), Daniele Cusi(University of Milan), Ian J. Deary(Harokopio University of Athens), George Dedoussis(Erasmus MC), Cornelia M. van Duijn(Erasmus MC), Johan G. Eriksson(University of Helsinki), Barbara Franke(University Medical Center Groningen), Lude Franke(University Medical Center Groningen), Paolo Gasparini(NorthShore University HealthSystem), Pablo V. Gejman(NorthShore University HealthSystem), Christian Gieger(Universitätsmedizin Greifswald), Hans J. Grabe(The University of Queensland), Jacob Gratten(The University of Queensland), Patrick J. F. Groenen(University of Iceland), Vilmundur Guðnason(University Medical Center Groningen), Pim van der Harst(University Medical Center Groningen), Wolfgang Hoffmann(University of South Australia), Elina Hyppönen(University of Minnesota), William G. Iacono(University of Minnesota), Bo Jacobsson(Norwegian Institute of Public Health), Marjo‐Riitta Järvelin(Oulu University Hospital), Karl‐Heinz Jöckel(Finnish Institute for Health and Welfare), Jaakko Kaprio(University of Helsinki), Sharon L. R. Kardia(Tampere University), Terho Lehtimäki(Tampere University), Steven F. Lehrer(National Bureau of Economic Research), Nicholas G. Martin(University of Minnesota), Matt McGue(University of Minnesota), Andres Metspalu(University of Manchester), Neil Pendleton(University of Manchester), Brenda W.J.H. Penninx(Finnish Institute for Health and Welfare), Markus Perola(University of Trieste), Nicola Pirastu(University of Trieste), Mario Pirastu(Institute of Genetic and Biomedical Research), Ozren Polašek(Amsterdam UMC Location Vrije Universiteit Amsterdam), Daniëlle Posthuma(South Australian Health and Medical Research Institute), Christopher Power(Washington University in St. Louis), Michael A. Province(University of Leicester), Nilesh J. Samani(University of Leicester), David Schlessinger(Medical University of Graz), Reinhold Schmidt(Medical University of Graz), Thorkild I. A. Sørensen(University of Copenhagen), Tim D. Spector(deCODE Genetics (Iceland)), Kāri Stefánsson(deCODE Genetics (Iceland)), Unnur Þorsteinsdóttir(deCODE Genetics (Iceland)), Roy Thurik(University of Bristol), Nicholas J. Timpson(Erasmus MC), Henning Tiemeier(Erasmus MC), André G. Uitterlinden(Western General Hospital), Véronique Vitart(Western General Hospital), Péter Vollenweider(University of Michigan), David R. Weir(University of Michigan), James F. Wilson(Western General Hospital), Alan F. Wright(Princeton University), Dalton Conley(University of Minnesota), Robert F. Krueger(University of Minnesota), George Davey Smith(Erasmus MC), Albert Hofman(Harvard University), David Laibson(Harvard University), Sarah E. Medland(The University of Queensland), Jian Yang(Rush University Medical Center), Tõnu Esko(University of Tartu), Chelsea Watson(Anderson University - South Carolina), Jonathan Jala(Princeton University), Dalton Conley(University of Wisconsin–Madison), Philipp Koellinger(University of Wisconsin–Madison), Magnus Johannesson(Harvard University), David Laibson(Harvard University), Michelle N. Meyer(University of Minnesota), James J. Lee(University of Minnesota), Augustine Kong(The University of Queensland), Loïc Yengo(The University of Queensland), David Cesarini(University of Southern California), Patrick Turley(University of Southern California), Peter M. Visscher(George Mason University), Jonathan Beauchamp(University of California, Los Angeles), Daniel J. Benjamin(National Bureau of Economic Research), Alexander I. Young(University of California, Los Angeles)
Cited by 681Open Access
Abstract
We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57.
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