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

Okbay A Beauchamp JP Fontana MA Lee JJ Pers TH Rietveld CA Turley P Chen GB Emilsson V Meddens SF Oskarsson S Pickrell JK Thom K Timshel P de Vlaming R Abdellaoui A Ahluwalia TS Bacelis J Baumbach C Bjornsdottir G Brandsma JH Pina Concas M Derringer J Furlotte NA Galesloot TE Girotto G Gupta R Hall LM Harris SE Hofer E Horikoshi M Huffman JE Kaasik K Kalafati IP Karlsson R Kong A Lahti J van der Lee SJ deLeeuw C Lind PA Lindgren KO Liu T Mangino M Marten J Mihailov E Miller MB van der Most PJ Oldmeadow C Payton A Pervjakova N Peyrot WJ Qian Y Raitakari O Rueedi R Salvi E Schmidt B Schraut KE Shi J Smith AV Poot RA St Pourcain B Teumer A Thorleifsson G Verweij N Vuckovic D Wellmann J Westra HJ Yang J Zhao W Zhu Z Alizadeh BZ Amin N Bakshi A Baumeister SE Biino G Bønnelykke K Boyle PA Campbell H Cappuccio FP Davies G De Neve JE Deloukas P Demuth I Ding J Eibich P Eisele L Eklund N Evans DM Faul JD Feitosa MF Forstner AJ Gandin I Gunnarsson B Halldórsson BV Harris TB Heath AC Hocking LJ Holliday EG Homuth G Horan MA Hottenga JJ de Jager PL Joshi PK Jugessur A Kaakinen MA Kähönen M Kanoni S KeltigangasJärvinen L Kiemeney LA Kolcic I Koskinen S Kraja AT Kroh M Kutalik Z Latvala A Launer LJ Lebreton MP Levinson DF Lichtenstein P Lichtner, P Liewald DC; LifeLines Cohort Study Loukola A Madden PA Mägi R MäkiOpas T Marioni RE MarquesVidal P Meddens GA McMahon G Meisinger C Meitinger T Milaneschi Y Milani L Montgomery GW Myhre R Nelson CP Nyholt DR Ollier WE Palotie A Paternoster L Pedersen NL Petrovic KE Porteous DJ Räikkönen K Ring SM Robino A Rostapshova O Rudan I Rustichini A Salomaa V Sanders AR Sarin AP Schmidt H Scott RJ Smith BH Smith JA Staessen JA SteinhagenThiessen E Strauch K Terracciano A Tobin MD Ulivi S Vaccargiu S Quaye L van Rooij FJ Venturini C Vinkhuyzen AA Völker U Völzke H Vonk JM Vozzi D Waage J Ware EB Willemsen G Attia JR Bennett DA Berger K Bertram L Bisgaard H Boomsma DI Borecki IB Bültmann U Chabris CF Cucca F Cusi D Deary IJ Dedoussis GV van Duijn CM Eriksson JG Franke B Franke L Gasparini P Gejman PV Gieger C Grabe HJ Gratten J Groenen PJ Gudnason V van der Harst P Hayward C Hinds DA Hoffmann W Hyppönen E Iacono WG Jacobsson B Järvelin MR Jöckel KH Kaprio J Kardia SL Lehtimäki T Lehrer SF Magnusson PK Martin NG McGue M Metspalu A Pendleton N Penninx BW Perola M Pirastu N Pirastu M Polasek O Posthuma D Power C Province MA Samani NJ Schlessinger D Schmidt R Sørensen TI Spector TD Stefansson K Thorsteinsdottir U Thurik AR Timpson NJ Tiemeier H Tung JY Uitterlinden AG Vitart V Vollenweider P Weir DR Wilson JF Wright AF Conley DC Krueger RF Davey Smith G Hofman A Laibson DI Medland SE Meyer MN Yang J Johannesson M Visscher PM Esko T Koellinger PD Cesarini, D Benjamin DJ

doi:10.1038/nature17671

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.