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

Okbay, A.; Beauchamp, J.P.; Fontana, M.A.; Lee, J.J.; Pers, T.H.; Rietveld, C.A.; Turley, P.; Chen, G.; Emilsson, V.; Meddens, S..F.W.; Oskarsson, S.; Pickrell, J.K.; Thom, K.; Timshel, P.; De Vlaming, R.; Abdellaoui, A.; Ahluwalia, T.S.; Bacelis, J.; Baumbach, C.; Bjornsdottir, G.; Brandsma, J.H.; Pina Concas, M.; Derringer, J.; Furlotte, N.A.; Galesloot, T.E.; Girotto, G.; Gupta, R.; Hall, L.M.; Harris, S.E.; Hofer, E.; Horikoshi, M.; Huffman, J.E.; Kaasik, K.; Kalafati, I.P.; Karlsson, R.; Kong, A.; Lahti, J.; Van Der Lee, S.J.; Deleeuw, C.; Lind, P.A.; Lindgren, K.; Liu, T.; Mangino, M.; Marten, J.; Mihailov, E.; Miller, M.B.; Van Der Most, P.J.; Oldmeadow, C.; Payton, A.; Pervjakova, N.; Peyrot, W.J.; Qian, Y.; Raitakari, O.; Rueedi, R.; Salvi, E.; Schmidt, B.; Schraut, K.E.; Shi, J.; Smith, A.V.; Poot, R.A.; St Pourcain, B.; Teumer, A.; Thorleifsson, G.; Verweij, N.; Vuckovic, D.; Wellmann, J.; Westra, H.; Yang, J.; Zhao, W.; Zhu, Z.; Alizadeh, B.Z.; Amin, N.; Bakshi, A.; Baumeister, S.E.; Biino, G.; Bønnelykke, K.; Boyle, P.A.; Campbell, H.; Cappuccio, F.P.; Davies, G.; De Neve, J.; Deloukas, P.; Demuth, I.; Ding, J.; Eibich, P.; Eisele, L.; Eklund, N.; Evans, D.M.; Faul, J.D.; Feitosa, M.F.; Forstner, A.J.; Gandin, I.; Gunnarsson, B.; Halldórsson, B.V.; Harris, T.B.; Holliday, E.G.; Heath, A.C.; Hocking, L.J.; Homuth, G.; Horan, M.A.; Hottenga, J.; De Jager, P.L.; Joshi, P.K.; Jugessur, A.; Kaakinen, M.A.; Kähönen, M.; Kanoni, S.; Keltigangas Järvinen, L.; Kiemeney, L.A..L..M.; Kolcic, I.; Koskinen, S.; Kraja, A.T.; Kroh, M.; Kutalik, Z.; Latvala, A.; Launer, L.J.; Lebreton, M.P.; Levinson, D.F.; Lichtenstein, P.; Lichtner, P.; Liewald, D.C..M.; Loukola, A.; Madden, P.A.; Mägi, R.; Mäki Opas, T.; Marioni, R.E.; Marques Vidal, P.; Meddens, G.A.; Mcmahon, G.; Meisinger, C.; Meitinger, T.; Milaneschi, Y.; Milani, L.; Montgomery, G.W.; Myhre, R.; Nelson, C.P.; Nyholt, D.R.; Ollier, W.E..R.; Palotie, A.; Paternoster, L.; Pedersen, N.L.; Petrovic, K.E.; Porteous, D.J.; Raïkkönen, K.; Ring, S.M.; Robino, A.; Rostapshova, O.; Rudan, I.; Rustichini, A.; Salomaa, V.; Sanders, A.R.; Sarin, A.; Schmidt, H.; Scott, R.J.; Smith, B.H.; Smith, J.A.; Staessen, J.A.; Steinhagen Thiessen, E.; Strauch, K.; Terracciano, A.; Tobin, M.D.; Ulivi, S.; Vaccargiu, S.; Quaye, L.; Van Rooij, F.J..A.; Venturini, C.; Vinkhuyzen, A.A..E.; Völker, U.; Völzke, H.; Vonk, J.M.; Vozzi, D.; Waage, J.; Ware, E.B.; Willemsen, G.; Attia, J.R.; Bennett, D.A.; Berger, K.; Bertram, L.; Bisgaard, H.; Boomsma, D.I.; Borecki, I.B.; Bültmann, U.; Chabris, C.F.; Cucca, F.; Cusi, D.; Deary, I.J.; Dedoussis, G.V.; Van Duijn, C.M.; Eriksson, J.G.; Franke, B.; Franke, L.; Gasparini, P.; Gejman, P.V.; Gieger, C.; Grabe, H.; Gratten, J.; Groenen, P.J..F.; Gudnason, V.; Van Der Harst, P.; Hayward, C.; Hinds, D.A.; Hoffmann, W.; Hyppönen, E.; Iacono, W.G.; Jacobsson, B.; Järvelin, M.; Jöckel, K.; Kaprio, J.; Kardia, S.L..R.; Lehtimäki, T.; Lehrer, S.F.; Magnusson, P.K..E.; Martin, N.G.; Mcgue, M.; Metspalu, A.; Pendleton, N.; Penninx, B.W..J..H.; Perola, M.; Pirastu, N.; Pirastu, M.; Polasek, O.; Posthuma, D.; Power, C.; Province, M.A.; Samani, N.J.; Schlessinger, D.; Schmidt, R.; Sørensen, T.I..A.; Spector, T.D.; Stefansson, K.; Thorsteinsdottir, U.; Thurik, A..R.; Timpson, N.J.; Tiemeier, H.; Tung, J.Y.; Uitterlinden, A.G.; Vitart, V.; Vollenweider, P.; Weir, D.R.; Wilson, J.F.; Wright, A.F.; Conley, D.C.; Krueger, R.F.; Davey Smith, G.; Hofman, A.; Laibson, D.I.; Medland, S.E.; Meyer, M.N.; Yang, J.; Johannesson, M.; Visscher, P.M.; Esko, T.; Koellinger, P.D.; Cesarini, D.; Benjamin, D.J.

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.

Genome-wide association study identifies 74 loci associated with educational attainment / A. Okbay, J.P. Beauchamp, M.A. Fontana, J.J. Lee, T.H. Pers, C.A. Rietveld, P. Turley, G. Chen, V. Emilsson, S..F.W. Meddens, S. Oskarsson, J.K. Pickrell, K. Thom, P. Timshel, R. De Vlaming, A. Abdellaoui, T.S. Ahluwalia, J. Bacelis, C. Baumbach, G. Bjornsdottir, J.H. Brandsma, M. Pina Concas, J. Derringer, N.A. Furlotte, T.E. Galesloot, G. Girotto, R. Gupta, L.M. Hall, S.E. Harris, E. Hofer, M. Horikoshi, J.E. Huffman, K. Kaasik, I.P. Kalafati, R. Karlsson, A. Kong, J. Lahti, S.J. Van Der Lee, C. Deleeuw, P.A. Lind, K. Lindgren, T. Liu, M. Mangino, J. Marten, E. Mihailov, M.B. Miller, P.J. Van Der Most, C. Oldmeadow, A. Payton, N. Pervjakova, W.J. Peyrot, Y. Qian, O. Raitakari, R. Rueedi, E. Salvi, B. Schmidt, K.E. Schraut, J. Shi, A.V. Smith, R.A. Poot, B. St Pourcain, A. Teumer, G. Thorleifsson, N. Verweij, D. Vuckovic, J. Wellmann, H. Westra, J. Yang, W. Zhao, Z. Zhu, B.Z. Alizadeh, N. Amin, A. Bakshi, S.E. Baumeister, G. Biino, K. Bønnelykke, P.A. Boyle, H. Campbell, F.P. Cappuccio, G. Davies, J. De Neve, P. Deloukas, I. Demuth, J. Ding, P. Eibich, L. Eisele, N. Eklund, D.M. Evans, J.D. Faul, M.F. Feitosa, A.J. Forstner, I. Gandin, B. Gunnarsson, B.V. Halldórsson, T.B. Harris, E.G. Holliday, A.C. Heath, L.J. Hocking, G. Homuth, M.A. Horan, J. Hottenga, P.L. De Jager, P.K. Joshi, A. Jugessur, M.A. Kaakinen, M. Kähönen, S. Kanoni, L. Keltigangas Järvinen, L.A..L..M. Kiemeney, I. Kolcic, S. Koskinen, A.T. Kraja, M. Kroh, Z. Kutalik, A. Latvala, L.J. Launer, M.P. Lebreton, D.F. Levinson, P. Lichtenstein, P. Lichtner, D.C..M. Liewald, A. Loukola, P.A. Madden, R. Mägi, T. Mäki Opas, R.E. Marioni, P. Marques Vidal, G.A. Meddens, G. Mcmahon, C. Meisinger, T. Meitinger, Y. Milaneschi, L. Milani, G.W. Montgomery, R. Myhre, C.P. Nelson, D.R. Nyholt, W.E..R. Ollier, A. Palotie, L. Paternoster, N.L. Pedersen, K.E. Petrovic, D.J. Porteous, K. Raïkkönen, S.M. Ring, A. Robino, O. Rostapshova, I. Rudan, A. Rustichini, V. Salomaa, A.R. Sanders, A. Sarin, H. Schmidt, R.J. Scott, B.H. Smith, J.A. Smith, J.A. Staessen, E. Steinhagen Thiessen, K. Strauch, A. Terracciano, M.D. Tobin, S. Ulivi, S. Vaccargiu, L. Quaye, F.J..A. Van Rooij, C. Venturini, A.A..E. Vinkhuyzen, U. Völker, H. Völzke, J.M. Vonk, D. Vozzi, J. Waage, E.B. Ware, G. Willemsen, J.R. Attia, D.A. Bennett, K. Berger, L. Bertram, H. Bisgaard, D.I. Boomsma, I.B. Borecki, U. Bültmann, C.F. Chabris, F. Cucca, D. Cusi, I.J. Deary, G.V. Dedoussis, C.M. Van Duijn, J.G. Eriksson, B. Franke, L. Franke, P. Gasparini, P.V. Gejman, C. Gieger, H. Grabe, J. Gratten, P.J..F. Groenen, V. Gudnason, P. Van Der Harst, C. Hayward, D.A. Hinds, W. Hoffmann, E. Hyppönen, W.G. Iacono, B. Jacobsson, M. Järvelin, K. Jöckel, J. Kaprio, S.L..R. Kardia, T. Lehtimäki, S.F. Lehrer, P.K..E. Magnusson, N.G. Martin, M. Mcgue, A. Metspalu, N. Pendleton, B.W..J..H. Penninx, M. Perola, N. Pirastu, M. Pirastu, O. Polasek, D. Posthuma, C. Power, M.A. Province, N.J. Samani, D. Schlessinger, R. Schmidt, T.I..A. Sørensen, T.D. Spector, K. Stefansson, U. Thorsteinsdottir, A..R. Thurik, N.J. Timpson, H. Tiemeier, J.Y. Tung, A.G. Uitterlinden, V. Vitart, P. Vollenweider, D.R. Weir, J.F. Wilson, A.F. Wright, D.C. Conley, R.F. Krueger, G. Davey Smith, A. Hofman, D.I. Laibson, S.E. Medland, M.N. Meyer, J. Yang, M. Johannesson, P.M. Visscher, T. Esko, P.D. Koellinger, D. Cesarini, D.J. Benjamin. - In: NATURE. - ISSN 0028-0836. - 533:7604(2016), pp. 539-542. [10.1038/nature17671]