Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals
Authors: Okbay Aysu , Wu Yeda , Wang Nancy , Jayashankar Hariharan , Bennett Michael , Nehzati Seyed Moeen , Sidorenko Julia , Kweon Hyeokmoon , Goldman Grant , Gjorgjieva Tamara , Jiang Yunxuan , Hicks Barry , Tian Chao , Hinds David A. , Ahlskog Rafael , Magnusson Patrik K. E. , Oskarsson Sven , Hayward Caroline , Campbell Archie , Porteous David J. , Freese Jeremy , Herd Pamela ,   23andMe Research Team, Agee Michelle , Alipanahi Babak , Auton Adam , Bell Robert K. , Bryc Katarzyna , Elson Sarah L. , Fontanillas Pierre , Furlotte Nicholas A. , Hinds David A. , Huber Karen E. , Kleinman Aaron , Litterman Nadia K. , McCreight Jennifer C. , McIntyre Matthew H. , Mountain Joanna L. , Northover Carrie A. M. , Pitts Steven J. , Sathirapongsasuti J. Fah , Sazonova Olga V. , Shelton Janie F. , Shringarpure Suyash , Tung Joyce Y. , Vacic Vladimir , Wilson Catherine H. ,   Social Science Genetic Association Consortium, Fontana Mark Alan , Pers Tune H. , Rietveld Cornelius A. , Chen Guo-Bo , Emilsson Valur , Meddens S. Fleur W. , Pickrell Joseph K. , Thom Kevin , Timshel Pascal , de Vlaming Ronald , Abdellaoui Abdel , Ahluwalia Tarunveer S. , Bacelis Jonas , Baumbach Clemens , Bjornsdottir Gyda , Brandsma Johannes H. , Concas Maria Pina , Derringer Jaime , Galesloot Tessel E. , Girotto Giorgia , Gupta Richa , Hall Leanne M. , Harris Sarah E. , Hofer Edith , Horikoshi Momoko , Huffman Jennifer E. , Kaasik Kadri , Kalafati Ioanna P. , Karlsson Robert , Lahti Jari , van der Lee Sven J. , de Leeuw Christiaan , Lind Penelope A. , Lindgren Karl-Oskar , Liu Tian , Mangino Massimo , Marten Jonathan , Mihailov Evelin , Miller Michael B. , van der Most Peter J. , Oldmeadow Christopher , Payton Antony , Pervjakova Natalia , Peyrot Wouter J. , Qian Yong , Raitakari Olli , Rueedi Rico , Salvi Erika , Schmidt Börge , Schraut Katharina E. , Shi Jianxin , Smith Albert V. , Poot Raymond A. , Pourcain Beate St , Teumer Alexander , Thorleifsson Gudmar , Verweij Niek , Vuckovic Dragana , Wellmann Juergen , Westra Harm-Jan , Yang Jingyun , Zhao Wei , Zhu Zhihong , Alizadeh Behrooz Z. , Amin Najaf , Bakshi Andrew , Baumeister Sebastian E. , Biino Ginevra , Bønnelykke Klaus , Boyle Patricia A. , Campbell Harry , Cappuccio Francesco P. , Davies Gail , De Neve Jan-Emmanuel , Deloukas Panos , Demuth Ilja , Ding Jun , Eibich Peter , Eisele Lewin , Eklund Niina , Evans David M. , Faul Jessica D. , Feitosa Mary F. , Forstner Andreas J. , Gandin Ilaria , Gunnarsson Bjarni , Halldórsson Bjarni V. , Harris Tamara B. , Heath Andrew C. , Hocking Lynne J. , Holliday Elizabeth G. , Homuth Georg , Horan Michael A. , Hottenga Jouke-Jan , de Jager Philip L. , Joshi Peter K. , Jugessur Astanand , Kaakinen Marika A. , Kähönen Mika , Kanoni Stavroula , Keltigangas-Järvinen Liisa , Kiemeney Lambertus A. L. M. , Kolcic Ivana , Koskinen Seppo , Kraja Aldi T. , Kroh Martin , Kutalik Zoltan , Latvala Antti , Launer Lenore J. , Lebreton Maël P. , Levinson Douglas F. , Lichtenstein Paul , Lichtner Peter , Liewald David C. M. ,   LifeLines Cohort Study, Loukola Anu , Madden Pamela A. , Mägi Reedik , Mäki-Opas Tomi , Marioni Riccardo E. , Marques-Vidal Pedro , Meddens Gerardus A. , McMahon George , Meisinger Christa , Meitinger Thomas , Milaneschi Yusplitri , Milani Lili , Montgomery Grant W. , Myhre Ronny , Nelson Christopher P. , Nyholt Dale R. , Ollier William E. R. , Palotie Aarno , Paternoster Lavinia , Pedersen Nancy L. , Petrovic Katja E. , Räikkönen Katri , Ring Susan M. , Robino Antonietta , Rostapshova Olga , Rudan Igor , Rustichini Aldo , Salomaa Veikko , Sanders Alan R. , Sarin Antti-Pekka , Schmidt Helena , Scott Rodney J. , Smith Blair H. , Smith Jennifer A. , Staessen Jan A. , Steinhagen-Thiessen Elisabeth , Strauch Konstantin , Terracciano Antonio , Tobin Martin D. , Ulivi Sheila , Vaccargiu Simona , Quaye Lydia , van Rooij Frank J. A. , Venturini Cristina , Vinkhuyzen Anna A. E. , Völker Uwe , Völzke Henry , Vonk Judith M. , Vozzi Diego , Waage Johannes , Ware Erin B. , Willemsen Gonneke , Attia John R. , Bennett David A. , Berger Klaus , Bertram Lars , Bisgaard Hans , Boomsma Dorret I. , Borecki Ingrid B. , Bültmann Ute , Chabris Christopher F. , Cucca Francesco , Cusi Daniele , Deary Ian J. , Dedoussis George V. , van Duijn Cornelia M. , Eriksson Johan G. , Franke Barbara , Franke Lude , Gasparini Paolo , Gejman Pablo V. , Gieger Christian , Grabe Hans-Jörgen , Gratten Jacob , Groenen Patrick J. F. , Gudnason Vilmundur , van der Harst Pim , Hoffmann Wolfgang , Hyppönen Elina , Iacono William G. , Jacobsson Bo , Järvelin Marjo-Riitta , Jöckel Karl-Heinz , Kaprio Jaakko , Kardia Sharon L. R. , Lehtimäki Terho , Lehrer Steven F. , Martin Nicholas G. , McGue Matt , Metspalu Andres , Pendleton Neil , Penninx Brenda W. J. H. , Perola Markus , Pirastu Nicola , Pirastu Mario , Polasek Ozren , Posthuma Danielle , Power Christine , Province Michael A. , Samani Nilesh J. , Schlessinger David , Schmidt Reinhold , Sørensen Thorkild I. A. , Spector Tim D. , Stefansson Kari , Thorsteinsdottir Unnur , Thurik A. Roy , Timpson Nicholas J. , Tiemeier Henning , Uitterlinden André G. , Vitart Veronique , Vollenweider Peter , Weir David R. , Wilson James F. , Wright Alan F. , Conley Dalton C. , Krueger Robert F. , Smith George Davey , Hofman Albert , Laibson David I. , Medland Sarah E. , Yang Jian , Esko Tõnu , Watson Chelsea , Jala Jonathan , Conley Dalton , Koellinger Philipp D. , Johannesson Magnus , Laibson David , Meyer Michelle N. , Lee James J. , Kong Augustine , Yengo Loic , Cesarini David , Turley Patrick , Visscher Peter M. , Beauchamp Jonathan P. , Benjamin Daniel J. , Young Alexander I. 
Published: March 2022

AbstractWe 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.