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

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; Elizabeth G. Holliday; Andrew C. Heath; Lynne J. Hocking; 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 Raïkkönen; 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; Toñu Esko; Philipp D. Koellinger; David Cesarini; Daniel J. Benjamin

doi:10.1038/nature17671

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

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 BjornsdottirJohannes 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, Elizabeth G. Holliday, Andrew C. Heath, Lynne J. Hocking, 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 Raïkkönen, 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, Toñu Esko, Philipp D. Koellinger, David Cesarini, Daniel J. Benjamin

Research output: Contribution to journal › Article › peer-review

691 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	539-542
Number of pages	4
Journal	Nature
Volume	533
Issue number	7604
DOIs	https://doi.org/10.1038/nature17671
State	Published - May 11 2016

Bibliographical note

Funding Information:
This study was supported by funding from the Ragnar Söderberg Foundation (E9/11), the Swedish Research Council (421-2013-1061), The Jan Wallander and Tom Hedelius Foundation, an ERC Consolidator Grant (647648 EdGe), the Pershing Square Fund of the Foundations of Human Behavior, and the NIA/NIH through grants P01-AG005842, P01-AG005842-20S2, P30-AG012810, and T32-AG000186-23 to NBER, and R01-AG042568 to USC.

Publisher Copyright:
© 2016 Macmillan Publishers Limited.

Publisher link

10.1038/nature17671

http://hdl.handle.net/10044/1/45793

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Okbay, A., Beauchamp, J. P., Fontana, M. A., Lee, J. J., Pers, T. H., Rietveld, C. A., Turley, P., Chen, G. B., 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., ... Benjamin, D. J. (2016). Genome-wide association study identifies 74 loci associated with educational attainment. Nature, 533(7604), 539-542. https://doi.org/10.1038/nature17671

Okbay, A, Beauchamp, JP, Fontana, MA, Lee, JJ, Pers, TH, Rietveld, CA, Turley, P, Chen, GB, Emilsson, V, Meddens, SFW, 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, Holliday, EG, Heath, AC, Hocking, LJ, Homuth, G, Horan, MA, Hottenga, JJ, De Jager, PL, Joshi, PK, Jugessur, A, Kaakinen, MA, Kähönen, M, Kanoni, S, Keltigangas-Järvinen, L, Kiemeney, LALM, Kolcic, I, Koskinen, S, Kraja, AT, Kroh, M, Kutalik, Z, Latvala, A, Launer, LJ, Lebreton, MP, Levinson, DF, Lichtenstein, P, Lichtner, P, Liewald, DCM, Loukola, A, Madden, PA, Mägi, R, Mäki-Opas, T, Marioni, RE, Marques-Vidal, P, Meddens, GA, Mcmahon, G, Meisinger, C, Meitinger, T, Milaneschi, Y, Milani, L, Montgomery, GW, Myhre, R, Nelson, CP, Nyholt, DR, Ollier, WER, Palotie, A, Paternoster, L, Pedersen, NL, Petrovic, KE, Porteous, DJ, Raïkkönen, 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, Steinhagen-Thiessen, E, Strauch, K, Terracciano, A, Tobin, MD, Ulivi, S, Vaccargiu, S, Quaye, L, Van Rooij, FJA, Venturini, C, Vinkhuyzen, AAE, 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, PJF, 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, SLR, Lehtimäki, T, Lehrer, SF, Magnusson, PKE, Martin, NG, Mcgue, M, Metspalu, A, Pendleton, N, Penninx, BWJH, Perola, M, Pirastu, N, Pirastu, M, Polasek, O, Posthuma, D, Power, C, Province, MA, Samani, NJ, Schlessinger, D, Schmidt, R, Sørensen, TIA, 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 2016, 'Genome-wide association study identifies 74 loci associated with educational attainment', Nature, vol. 533, no. 7604, pp. 539-542. https://doi.org/10.1038/nature17671

@article{61436c15db3e4743b5dc86fa14ceeca6,

title = "Genome-wide association study identifies 74 loci associated with educational attainment",

abstract = "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.",

author = "Aysu Okbay and Beauchamp, {Jonathan P.} and Fontana, {Mark Alan} and Lee, {James J.} and Pers, {Tune H.} and Rietveld, {Cornelius A.} and Patrick Turley and Chen, {Guo Bo} and Valur Emilsson and Meddens, {S. Fleur W} and Sven Oskarsson and Pickrell, {Joseph K.} and Kevin Thom and Pascal Timshel and {De Vlaming}, Ronald and Abdel Abdellaoui and Ahluwalia, {Tarunveer S.} and Jonas Bacelis and Clemens Baumbach and Gyda Bjornsdottir and Brandsma, {Johannes H.} and {Pina Concas}, Maria and Jaime Derringer and Furlotte, {Nicholas A.} and Galesloot, {Tessel E.} and Giorgia Girotto and Richa Gupta and Hall, {Leanne M.} and Harris, {Sarah E.} and Edith Hofer and Momoko Horikoshi and Huffman, {Jennifer E.} and Kadri Kaasik and Kalafati, {Ioanna P.} and Robert Karlsson and Augustine Kong and Jari Lahti and {Van Der Lee}, {Sven J.} and Christiaan Deleeuw and Lind, {Penelope A.} and Lindgren, {Karl Oskar} and Tian Liu and Massimo Mangino and Jonathan Marten and Evelin Mihailov and Miller, {Michael B.} and {Van Der Most}, {Peter J.} and Christopher Oldmeadow and Antony Payton and Natalia Pervjakova and Peyrot, {Wouter J.} and Yong Qian and Olli Raitakari and Rico Rueedi and Erika Salvi and B{\"o}rge Schmidt and Schraut, {Katharina E.} and Jianxin Shi and Smith, {Albert V.} and Poot, {Raymond A.} and {St Pourcain}, Beate and Alexander Teumer and Gudmar Thorleifsson and Niek Verweij and Dragana Vuckovic and Juergen Wellmann and Westra, {Harm Jan} and Jingyun Yang and Wei Zhao and Zhihong Zhu and Alizadeh, {Behrooz Z.} and Najaf Amin and Andrew Bakshi and Baumeister, {Sebastian E.} and Ginevra Biino and Klaus B{\o}nnelykke and Boyle, {Patricia A.} and Harry Campbell and Cappuccio, {Francesco P.} and Gail Davies and {De Neve}, {Jan Emmanuel} and Panos Deloukas and Ilja Demuth and Jun Ding and Peter Eibich and Lewin Eisele and Niina Eklund and Evans, {David M.} and Faul, {Jessica D.} and Feitosa, {Mary F.} and Forstner, {Andreas J.} and Ilaria Gandin and Bjarni Gunnarsson and Halld{\'o}rsson, {Bjarni V.} and Harris, {Tamara B.} and Holliday, {Elizabeth G.} and Heath, {Andrew C.} and Hocking, {Lynne J.} and Georg Homuth and Horan, {Michael A.} and Hottenga, {Jouke Jan} and {De Jager}, {Philip L.} and Joshi, {Peter K.} and Astanand Jugessur and Kaakinen, {Marika A.} and Mika K{\"a}h{\"o}nen and Stavroula Kanoni and Liisa Keltigangas-J{\"a}rvinen and Kiemeney, {Lambertus A L M} and Ivana Kolcic and Seppo Koskinen and Kraja, {Aldi T.} and Martin Kroh and Zoltan Kutalik and Antti Latvala and Launer, {Lenore J.} and Lebreton, {Ma{\"e}l P.} and Levinson, {Douglas F.} and Paul Lichtenstein and Peter Lichtner and Liewald, {David C M} and Anu Loukola and Madden, {Pamela A.} and Reedik M{\"a}gi and Tomi M{\"a}ki-Opas and Marioni, {Riccardo E.} and Pedro Marques-Vidal and Meddens, {Gerardus A.} and George Mcmahon and Christa Meisinger and Thomas Meitinger and Yusplitri Milaneschi and Lili Milani and Montgomery, {Grant W.} and Ronny Myhre and Nelson, {Christopher P.} and Nyholt, {Dale R.} and Ollier, {William E R} and Aarno Palotie and Lavinia Paternoster and Pedersen, {Nancy L.} and Petrovic, {Katja E.} and Porteous, {David J.} and Katri Ra{\"i}kk{\"o}nen and Ring, {Susan M.} and Antonietta Robino and Olga Rostapshova and Igor Rudan and Aldo Rustichini and Veikko Salomaa and Sanders, {Alan R.} and Sarin, {Antti Pekka} and Helena Schmidt and Scott, {Rodney J.} and Smith, {Blair H.} and Smith, {Jennifer A.} and Staessen, {Jan A.} and Elisabeth Steinhagen-Thiessen and Konstantin Strauch and Antonio Terracciano and Tobin, {Martin D.} and Sheila Ulivi and Simona Vaccargiu and Lydia Quaye and {Van Rooij}, {Frank J A} and Cristina Venturini and Vinkhuyzen, {Anna A E} and Uwe V{\"o}lker and Henry V{\"o}lzke and Vonk, {Judith M.} and Diego Vozzi and Johannes Waage and Ware, {Erin B.} and Gonneke Willemsen and Attia, {John R.} and Bennett, {David A.} and Klaus Berger and Lars Bertram and Hans Bisgaard and Boomsma, {Dorret I.} and Borecki, {Ingrid B.} and Ute B{\"u}ltmann and Chabris, {Christopher F.} and Francesco Cucca and Daniele Cusi and Deary, {Ian J.} and Dedoussis, {George V.} and {Van Duijn}, {Cornelia M.} and Eriksson, {Johan G.} and Barbara Franke and Lude Franke and Paolo Gasparini and Gejman, {Pablo V.} and Christian Gieger and Grabe, {Hans J{\"o}rgen} and Jacob Gratten and Groenen, {Patrick J F} and Vilmundur Gudnason and {Van Der Harst}, Pim and Caroline Hayward and Hinds, {David A.} and Wolfgang Hoffmann and Elina Hypp{\"o}nen and Iacono, {William G.} and Bo Jacobsson and J{\"a}rvelin, {Marjo Riitta} and J{\"o}ckel, {Karl Heinz} and Jaakko Kaprio and Kardia, {Sharon L R} and Terho Lehtim{\"a}ki and Lehrer, {Steven F.} and Magnusson, {Patrik K E} and Martin, {Nicholas G.} and Matt Mcgue and Andres Metspalu and Neil Pendleton and Penninx, {Brenda W J H} and Markus Perola and Nicola Pirastu and Mario Pirastu and Ozren Polasek and Danielle Posthuma and Christine Power and Province, {Michael A.} and Samani, {Nilesh J.} and David Schlessinger and Reinhold Schmidt and S{\o}rensen, {Thorkild I A} and Spector, {Tim D.} and Kari Stefansson and Unnur Thorsteinsdottir and Thurik, {A. Roy} and Timpson, {Nicholas J.} and Henning Tiemeier and Tung, {Joyce Y.} and Uitterlinden, {Andr{\'e} G.} and Veronique Vitart and Peter Vollenweider and Weir, {David R.} and Wilson, {James F.} and Wright, {Alan F.} and Conley, {Dalton C.} and Krueger, {Robert F.} and {Davey Smith}, George and Albert Hofman and Laibson, {David I.} and Medland, {Sarah E.} and Meyer, {Michelle N.} and Jian Yang and Magnus Johannesson and Visscher, {Peter M.} and To{\~n}u Esko and Koellinger, {Philipp D.} and David Cesarini and Benjamin, {Daniel J.}",

note = "Funding Information: This study was supported by funding from the Ragnar S{\"o}derberg Foundation (E9/11), the Swedish Research Council (421-2013-1061), The Jan Wallander and Tom Hedelius Foundation, an ERC Consolidator Grant (647648 EdGe), the Pershing Square Fund of the Foundations of Human Behavior, and the NIA/NIH through grants P01-AG005842, P01-AG005842-20S2, P30-AG012810, and T32-AG000186-23 to NBER, and R01-AG042568 to USC. Publisher Copyright: {\textcopyright} 2016 Macmillan Publishers Limited.",

year = "2016",

month = may,

day = "11",

doi = "10.1038/nature17671",

language = "English (US)",

volume = "533",

pages = "539--542",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7604",

}

TY - JOUR

T1 - Genome-wide association study identifies 74 loci associated with educational attainment

AU - Okbay, Aysu

AU - Beauchamp, Jonathan P.

AU - Fontana, Mark Alan

AU - Lee, James J.

AU - Pers, Tune H.

AU - Rietveld, Cornelius A.

AU - Turley, Patrick

AU - Chen, Guo Bo

AU - Emilsson, Valur

AU - Meddens, S. Fleur W

AU - Oskarsson, Sven

AU - Pickrell, Joseph K.

AU - Thom, Kevin

AU - Timshel, Pascal

AU - De Vlaming, Ronald

AU - Abdellaoui, Abdel

AU - Ahluwalia, Tarunveer S.

AU - Bacelis, Jonas

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N1 - Funding Information: This study was supported by funding from the Ragnar Söderberg Foundation (E9/11), the Swedish Research Council (421-2013-1061), The Jan Wallander and Tom Hedelius Foundation, an ERC Consolidator Grant (647648 EdGe), the Pershing Square Fund of the Foundations of Human Behavior, and the NIA/NIH through grants P01-AG005842, P01-AG005842-20S2, P30-AG012810, and T32-AG000186-23 to NBER, and R01-AG042568 to USC. Publisher Copyright: © 2016 Macmillan Publishers Limited.

PY - 2016/5/11

Y1 - 2016/5/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84969760786&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84969760786&partnerID=8YFLogxK

U2 - 10.1038/nature17671

DO - 10.1038/nature17671

M3 - Article

C2 - 27225129

AN - SCOPUS:84969760786

SN - 0028-0836

VL - 533

SP - 539

EP - 542

JO - Nature

JF - Nature

IS - 7604

ER -

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

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