Genome-wide association study identifies 74 loci associated with educational attainment.

Authors:
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 deLeeuw 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 Ginevra Biino Klaus Bønnelykke Patricia A Boyle Harry Campbell Francesco P Cappuccio Gail Davies Jan-Emmanuel De Neve Panos Deloukas Ilja Demuth Jun Ding Peter Eibich Lewin Eisele Niina Eklund David M Evans Jessica D Faul Mary F Feitosa Andreas J Forstner Ilaria Gandin Bjarni Gunnarsson Bjarni V Halldórsson Tamara B Harris Andrew C Heath Lynne J Hocking Elizabeth G Holliday Georg Homuth Michael A Horan Jouke-Jan Hottenga Philip L de Jager Peter K Joshi Astanand Jugessur Marika A Kaakinen Mika Kähönen Stavroula Kanoni Liisa Keltigangas-Järvinen Lambertus A L M Kiemeney Ivana Kolcic Seppo Koskinen Aldi T Kraja Martin Kroh Zoltan Kutalik Antti Latvala Lenore J Launer Maël P Lebreton Douglas F Levinson Paul Lichtenstein Peter Lichtner David C M Liewald Anu Loukola Pamela A Madden Reedik Mägi Tomi Mäki-Opas Riccardo E Marioni Pedro Marques-Vidal Gerardus A Meddens George McMahon Christa Meisinger Thomas Meitinger Yusplitri Milaneschi Lili Milani Grant W Montgomery Ronny Myhre Christopher P Nelson Dale R Nyholt William E R Ollier Aarno Palotie Lavinia Paternoster Nancy L Pedersen Katja E Petrovic David J Porteous Katri Räikkönen Susan M Ring Antonietta Robino Olga Rostapshova Igor Rudan Aldo Rustichini Veikko Salomaa Alan R Sanders Antti-Pekka Sarin Helena Schmidt Rodney J Scott Blair H Smith Jennifer A Smith Jan A Staessen Elisabeth Steinhagen-Thiessen Konstantin Strauch Antonio Terracciano Martin D Tobin Sheila Ulivi Simona Vaccargiu Lydia Quaye Frank J A van Rooij Cristina Venturini Anna A E Vinkhuyzen Uwe Völker Henry Völzke Judith M Vonk Diego Vozzi Johannes Waage Erin B Ware Gonneke Willemsen John R Attia David A Bennett Klaus Berger Lars Bertram Hans Bisgaard Dorret I Boomsma Ingrid B Borecki Ute Bültmann Christopher F Chabris Francesco Cucca Daniele Cusi Ian J Deary George V Dedoussis Cornelia M van Duijn Johan G Eriksson Barbara Franke Lude Franke Paolo Gasparini Pablo V Gejman Christian Gieger Hans-Jörgen Grabe Jacob Gratten Patrick J F Groenen Vilmundur Gudnason Pim van der Harst Caroline Hayward David A Hinds Wolfgang Hoffmann Elina Hyppönen William G Iacono Bo Jacobsson Marjo-Riitta Järvelin Karl-Heinz Jöckel Jaakko Kaprio Sharon L R Kardia Terho Lehtimäki Steven F Lehrer Patrik K E Magnusson Nicholas G Martin Matt McGue Andres Metspalu Neil Pendleton 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 Tim D Spector 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 Albert Hofman David I Laibson Sarah E Medland Michelle N Meyer Jian Yang Magnus Johannesson Peter M Visscher Tõnu Esko Philipp D Koellinger David Cesarini Daniel J Benjamin

Nature 2016 05 11;533(7604):539-42. Epub 2016 May 11.

Center for Economic and Social Research, University of Southern California, Los Angeles, California 90089-3332, USA.

Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.

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http://dx.doi.org/10.1038/nature17671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4883595PMC
May 2016

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