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

W. Peyrot; A.A.E. Vinkhuyzen; J.J. Hottenga; G. Willemsen; D.I. Boomsma; B.W.J.H. Penninx; D. Laibson; S.E. Medland; M.N. Meyer; J. Yang; M. Johannesson; P.M. Visscher; T. Esko; P.D. Koellinger; D. Cesarini; D.J. Benjamin; Christiaan de Leeuw; Yong Qian; Olli Raitakari; Rico Rueedi; Erika Salvi; Brge 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; Wei Zhao; Zhihong Zhu; Behrooz Z. Alizadeh; Najaf Amin; Andrew Bakshi; Sebastian E. Baumeister; Ginevra Biino; Klaus Bonnelykke; 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. Halldorsson; Tamara B. Harris; Andrew C. Heath; Lynne J. Hocking; Elizabeth G. Holliday; Georg Homuth; Michael A. Horan; Philip L. de Jager; Peter K. Joshi; Astanand Jugessur; Marika A. Kaakinen; Mika Kahonen; Stavroula Kanoni; Liisa Keltigangas-Jarvinen; Lambertus A. L. M. Kiemeney; Ivana Kolcic; Seppo Koskinen; Aldi T. Kraja; Martin Kroh; Zoltan Kutalik; Antti Latvala; Lenore J. Launer; Mael P. Lebreton; Douglas F. Levinson; Paul Lichtenstein; Peter Lichtner; David C. M. Liewald; Anu Loukola; Pamela A. Madden; Reedik Magi; Tomi Maki-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 Raikkonen; 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; Uwe Volker; Henry Volzke; Judith M. Vonk; Diego Vozzi; Johannes Waage; Erin B. Ware; John R. Attia; David A. Bennett; Klaus Berger; Lars Bertram; Hans Bisgaard; Ingrid B. Borecki; Ute Bultmann; 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-Jorgen Grabe; Jacob Gratten; Patrick J. F. Groenen; Vilmundur Gudnason; Pim van der Harst; Caroline Hayward; David A. Hinds; Wolfgang Hoffmann; Elina Hyppnen; William G. Iacono; Bo Jacobsson; Marjo-Riitta Jarvelin; Karl-Heinz Jockel; Jaakko Kaprio; Sharon L. R. Kardia; Terho Lehtimaki; Steven F. Lehrer; Patrik K. E. Magnusson; Nicholas G. Martin; Matt McGue; Andres Metspalu; Neil Pendleton; 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. Sorensen; Tim D. Spector; Kari Stefansson; Unnur Thorsteinsdottir; A. Roy Thurik; Nicholas J. Timpson; Henning Tiemeier; Joyce Y. Tung; Andre 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; Yuri Milaneschi; Social Science Genetic Association Consortium

doi:https://doi.org/10.1038/nature17671

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

W. Peyrot, A.A.E. Vinkhuyzen, J.J. Hottenga, G. Willemsen, D.I. Boomsma, B.W.J.H. Penninx, D. Laibson, S.E. Medland, M.N. Meyer, J. Yang, M. Johannesson, P.M. Visscher, T. Esko, P.D. Koellinger, D. Cesarini, D.J. Benjamin, Christiaan de Leeuw, Yong Qian, Olli Raitakari, Rico RueediErika Salvi, Brge 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, Wei Zhao, Zhihong Zhu, Behrooz Z. Alizadeh, Najaf Amin, Andrew Bakshi, Sebastian E. Baumeister, Ginevra Biino, Klaus Bonnelykke, 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. Halldorsson, Tamara B. Harris, Andrew C. Heath, Lynne J. Hocking, Elizabeth G. Holliday, Georg Homuth, Michael A. Horan, Philip L. de Jager, Peter K. Joshi, Astanand Jugessur, Marika A. Kaakinen, Mika Kahonen, Stavroula Kanoni, Liisa Keltigangas-Jarvinen, Lambertus A. L. M. Kiemeney, Ivana Kolcic, Seppo Koskinen, Aldi T. Kraja, Martin Kroh, Zoltan Kutalik, Antti Latvala, Lenore J. Launer, Mael P. Lebreton, Douglas F. Levinson, Paul Lichtenstein, Peter Lichtner, David C. M. Liewald, Anu Loukola, Pamela A. Madden, Reedik Magi, Tomi Maki-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 Raikkonen, 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, Uwe Volker, Henry Volzke, Judith M. Vonk, Diego Vozzi, Johannes Waage, Erin B. Ware, John R. Attia, David A. Bennett, Klaus Berger, Lars Bertram, Hans Bisgaard, Ingrid B. Borecki, Ute Bultmann, 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-Jorgen Grabe, Jacob Gratten, Patrick J. F. Groenen, Vilmundur Gudnason, Pim van der Harst, Caroline Hayward, David A. Hinds, Wolfgang Hoffmann, Elina Hyppnen, William G. Iacono, Bo Jacobsson, Marjo-Riitta Jarvelin, Karl-Heinz Jockel, Jaakko Kaprio, Sharon L. R. Kardia, Terho Lehtimaki, Steven F. Lehrer, Patrik K. E. Magnusson, Nicholas G. Martin, Matt McGue, Andres Metspalu, Neil Pendleton, 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. Sorensen, Tim D. Spector, Kari Stefansson, Unnur Thorsteinsdottir, A. Roy Thurik, Nicholas J. Timpson, Henning Tiemeier, Joyce Y. Tung, Andre 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, Yuri Milaneschi, Social Science Genetic Association Consortium

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

745 Citations (Scopus)

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
Pages (from-to)	539-542
Number of pages	4
Journal	NATURE
Volume	533
Issue number	7604
Early online date	11 May 2016
DOIs	https://doi.org/10.1038/nature17671
Publication status	Published - 26 May 2016

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https://doi.org/10.1038/nature17671

https://pure.uva.nl/ws/files/62735133/nature17671.pdf

Cite this

Peyrot, W., Vinkhuyzen, A. A. E., Hottenga, J. J., Willemsen, G., Boomsma, D. I., Penninx, B. W. J. H., Laibson, D., Medland, S. E., Meyer, M. N., Yang, J., Johannesson, M., Visscher, P. M., Esko, T., Koellinger, P. D., Cesarini, D., Benjamin, D. J., de Leeuw, C., Qian, Y., Raitakari, O., ... Social Science Genetic Association Consortium (2016). Genome-wide association study identifies 74 loci associated with educational attainment. NATURE, 533(7604), 539-542. Advance online publication. https://doi.org/10.1038/nature17671

@article{4fe4651f865e44828b65813298c94677,

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 = "A. Okbay and J. Beauchamp and M.A. Fontana and J.J. Lee and T.H. Pers and C.A. Rietveld and P. Turley and G.B. Chen and V. Emilsson and {de Vlaming}, R. and A. Abdellaoui and W. Peyrot and A.A.E. Vinkhuyzen and J.J. Hottenga and G. Willemsen and D.I. Boomsma and B.W.J.H. Penninx and D. Laibson and S.E. Medland and M.N. Meyer and J. Yang and M. Johannesson and P.M. Visscher and T. Esko and P.D. Koellinger and D. Cesarini and D.J. Benjamin and Meddens, {S. Fleur W.} and Sven Oskarsson and Pickrell, {Joseph K.} and Kevin Thom and Pascal Timshel and Ahluwalia, {Tarunveer S.} and Jonas Bacelis and Clemens Baumbach and Gyda Bjornsdottir and Brandsma, {Johannes H.} and Concas, {Maria Pina} 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 {de Leeuw}, Christiaan and Lind, {Penelope A.} and Karl-Oskar Lindgren 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 Yong Qian and Olli Raitakari and Rico Rueedi and Erika Salvi and Brge 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 Harm-Jan Westra 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 Bonnelykke 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 Halldorsson, {Bjarni V.} and Harris, {Tamara B.} and Heath, {Andrew C.} and Hocking, {Lynne J.} and Holliday, {Elizabeth G.} and Georg Homuth and Horan, {Michael A.} and {de Jager}, {Philip L.} and Joshi, {Peter K.} and Astanand Jugessur and Kaakinen, {Marika A.} and Mika Kahonen and Stavroula Kanoni and Liisa Keltigangas-Jarvinen 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, {Mael 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 Magi and Tomi Maki-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 Raikkonen and Ring, {Susan M.} and Antonietta Robino and Olga Rostapshova and Igor Rudan and Aldo Rustichini and Veikko Salomaa and Sanders, {Alan R.} and Antti-Pekka Sarin 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 Uwe Volker and Henry Volzke and Vonk, {Judith M.} and Diego Vozzi and Johannes Waage and Ware, {Erin B.} and Attia, {John R.} and Bennett, {David A.} and Klaus Berger and Lars Bertram and Hans Bisgaard and Borecki, {Ingrid B.} and Ute Bultmann 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 Hans-Jorgen Grabe 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 Hyppnen and Iacono, {William G.} and Bo Jacobsson and Marjo-Riitta Jarvelin and Karl-Heinz Jockel and Jaakko Kaprio and Kardia, {Sharon L. R.} and Terho Lehtimaki and Lehrer, {Steven F.} and Magnusson, {Patrik K. E.} and Martin, {Nicholas G.} and Matt McGue and Andres Metspalu and Neil Pendleton 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 Sorensen, {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, {Andre 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 Smith, {George Davey} and Albert Hofman and Yuri Milaneschi and {Social Science Genetic Association Consortium} and Christiaan Deleeuw",

note = "With supplementary information.",

year = "2016",

month = may,

day = "26",

doi = "https://doi.org/10.1038/nature17671",

language = "English",

volume = "533",

pages = "539--542",

journal = "NATURE",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7604",

}

Peyrot, W, Vinkhuyzen, AAE, Hottenga, JJ, Willemsen, G, Boomsma, DI, Penninx, BWJH, Laibson, D, Medland, SE, Meyer, MN, Yang, J, Johannesson, M, Visscher, PM, Esko, T, Koellinger, PD, Cesarini, D, Benjamin, DJ, de Leeuw, C, 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, H-J, Zhao, W, Zhu, Z, Alizadeh, BZ, Amin, N, Bakshi, A, Baumeister, SE, Biino, G, Bonnelykke, K, Boyle, PA, Campbell, H, Cappuccio, FP, Davies, G, De Neve, J-E, Deloukas, P, Demuth, I, Ding, J, Eibich, P, Eisele, L, Eklund, N, Evans, DM, Faul, JD, Feitosa, MF, Forstner, AJ, Gandin, I, Gunnarsson, B, Halldorsson, BV, Harris, TB, Heath, AC, Hocking, LJ, Holliday, EG, Homuth, G, Horan, MA, de Jager, PL, Joshi, PK, Jugessur, A, Kaakinen, MA, Kahonen, M, Kanoni, S, Keltigangas-Jarvinen, 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, Magi, R, Maki-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, Raikkonen, K, Ring, SM, Robino, A, Rostapshova, O, Rudan, I, Rustichini, A, Salomaa, V, Sanders, AR, Sarin, A-P, 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, Volker, U, Volzke, H, Vonk, JM, Vozzi, D, Waage, J, Ware, EB, Attia, JR, Bennett, DA, Berger, K, Bertram, L, Bisgaard, H, Borecki, IB, Bultmann, 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, H-J, Gratten, J, Groenen, PJF, Gudnason, V, van der Harst, P, Hayward, C, Hinds, DA, Hoffmann, W, Hyppnen, E, Iacono, WG, Jacobsson, B, Jarvelin, M-R, Jockel, K-H, Kaprio, J, Kardia, SLR, Lehtimaki, T, Lehrer, SF, Magnusson, PKE, Martin, NG, McGue, M, Metspalu, A, Pendleton, N, Perola, M, Pirastu, N, Pirastu, M, Polasek, O, Posthuma, D, Power, C, Province, MA, Samani, NJ, Schlessinger, D, Schmidt, R, Sorensen, 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, Smith, GD, Hofman, A, Milaneschi, Y & Social Science Genetic Association Consortium 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

TY - JOUR

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

AU - Okbay, A.

AU - Beauchamp, J.

AU - Fontana, M.A.

AU - Lee, J.J.

AU - Pers, T.H.

AU - Rietveld, C.A.

AU - Turley, P.

AU - Chen, G.B.

AU - Emilsson, V.

AU - de Vlaming, R.

AU - Abdellaoui, A.

AU - Peyrot, W.

AU - Vinkhuyzen, A.A.E.

AU - Hottenga, J.J.

AU - Willemsen, G.

AU - Boomsma, D.I.

AU - Penninx, B.W.J.H.

AU - Laibson, D.

AU - Medland, S.E.

AU - Meyer, M.N.

AU - Yang, J.

AU - Johannesson, M.

AU - Visscher, P.M.

AU - Esko, T.

AU - Koellinger, P.D.

AU - Cesarini, D.

AU - Benjamin, D.J.

AU - Meddens, S. Fleur W.

AU - Oskarsson, Sven

AU - Pickrell, Joseph K.

AU - Thom, Kevin

AU - Timshel, Pascal

AU - Ahluwalia, Tarunveer S.

AU - Bacelis, Jonas

AU - Baumbach, Clemens

AU - Bjornsdottir, Gyda

AU - Brandsma, Johannes H.

AU - Concas, Maria Pina

AU - Derringer, Jaime

AU - Furlotte, Nicholas A.

AU - Galesloot, Tessel E.

AU - Girotto, Giorgia

AU - Gupta, Richa

AU - Hall, Leanne M.

AU - Harris, Sarah E.

AU - Hofer, Edith

AU - Horikoshi, Momoko

AU - Huffman, Jennifer E.

AU - Kaasik, Kadri

AU - Kalafati, Ioanna P.

AU - Karlsson, Robert

AU - Kong, Augustine

AU - Lahti, Jari

AU - van der Lee, Sven J.

AU - de Leeuw, Christiaan

AU - Lind, Penelope A.

AU - Lindgren, Karl-Oskar

AU - Liu, Tian

AU - Mangino, Massimo

AU - Marten, Jonathan

AU - Mihailov, Evelin

AU - Miller, Michael B.

AU - van der Most, Peter J.

AU - Oldmeadow, Christopher

AU - Payton, Antony

AU - Pervjakova, Natalia

AU - Qian, Yong

AU - Raitakari, Olli

AU - Rueedi, Rico

AU - Salvi, Erika

AU - Schmidt, Brge

AU - Schraut, Katharina E.

AU - Shi, Jianxin

AU - Smith, Albert V.

AU - Poot, Raymond A.

AU - St Pourcain, Beate

AU - Teumer, Alexander

AU - Thorleifsson, Gudmar

AU - Verweij, Niek

AU - Vuckovic, Dragana

AU - Wellmann, Juergen

AU - Westra, Harm-Jan

AU - Zhao, Wei

AU - Zhu, Zhihong

AU - Alizadeh, Behrooz Z.

AU - Amin, Najaf

AU - Bakshi, Andrew

AU - Baumeister, Sebastian E.

AU - Biino, Ginevra

AU - Bonnelykke, Klaus

AU - Boyle, Patricia A.

AU - Campbell, Harry

AU - Cappuccio, Francesco P.

AU - Davies, Gail

AU - De Neve, Jan-Emmanuel

AU - Deloukas, Panos

AU - Demuth, Ilja

AU - Ding, Jun

AU - Eibich, Peter

AU - Eisele, Lewin

AU - Eklund, Niina

AU - Evans, David M.

AU - Faul, Jessica D.

AU - Feitosa, Mary F.

AU - Forstner, Andreas J.

AU - Gandin, Ilaria

AU - Gunnarsson, Bjarni

AU - Halldorsson, Bjarni V.

AU - Harris, Tamara B.

AU - Heath, Andrew C.

AU - Hocking, Lynne J.

AU - Holliday, Elizabeth G.

AU - Homuth, Georg

AU - Horan, Michael A.

AU - de Jager, Philip L.

AU - Joshi, Peter K.

AU - Jugessur, Astanand

AU - Kaakinen, Marika A.

AU - Kahonen, Mika

AU - Kanoni, Stavroula

AU - Keltigangas-Jarvinen, Liisa

AU - Kiemeney, Lambertus A. L. M.

AU - Kolcic, Ivana

AU - Koskinen, Seppo

AU - Kraja, Aldi T.

AU - Kroh, Martin

AU - Kutalik, Zoltan

AU - Latvala, Antti

AU - Launer, Lenore J.

AU - Lebreton, Mael P.

AU - Levinson, Douglas F.

AU - Lichtenstein, Paul

AU - Lichtner, Peter

AU - Liewald, David C. M.

AU - Loukola, Anu

AU - Madden, Pamela A.

AU - Magi, Reedik

AU - Maki-Opas, Tomi

AU - Marioni, Riccardo E.

AU - Marques-Vidal, Pedro

AU - Meddens, Gerardus A.

AU - McMahon, George

AU - Meisinger, Christa

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AU - Milaneschi, Yusplitri

AU - Milani, Lili

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AU - Myhre, Ronny

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AU - Palotie, Aarno

AU - Paternoster, Lavinia

AU - Pedersen, Nancy L.

AU - Petrovic, Katja E.

AU - Porteous, David J.

AU - Raikkonen, Katri

AU - Ring, Susan M.

AU - Robino, Antonietta

AU - Rostapshova, Olga

AU - Rudan, Igor

AU - Rustichini, Aldo

AU - Salomaa, Veikko

AU - Sanders, Alan R.

AU - Sarin, Antti-Pekka

AU - Schmidt, Helena

AU - Scott, Rodney J.

AU - Smith, Blair H.

AU - Smith, Jennifer A.

AU - Staessen, Jan A.

AU - Steinhagen-Thiessen, Elisabeth

AU - Strauch, Konstantin

AU - Terracciano, Antonio

AU - Tobin, Martin D.

AU - Ulivi, Sheila

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AU - Quaye, Lydia

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AU - Bultmann, Ute

AU - Chabris, Christopher F.

AU - Cucca, Francesco

AU - Cusi, Daniele

AU - Deary, Ian J.

AU - Dedoussis, George V.

AU - van Duijn, Cornelia M.

AU - Eriksson, Johan G.

AU - Franke, Barbara

AU - Franke, Lude

AU - Gasparini, Paolo

AU - Gejman, Pablo V.

AU - Gieger, Christian

AU - Grabe, Hans-Jorgen

AU - Gratten, Jacob

AU - Groenen, Patrick J. F.

AU - Gudnason, Vilmundur

AU - van der Harst, Pim

AU - Hayward, Caroline

AU - Hinds, David A.

AU - Hoffmann, Wolfgang

AU - Hyppnen, Elina

AU - Iacono, William G.

AU - Jacobsson, Bo

AU - Jarvelin, Marjo-Riitta

AU - Jockel, Karl-Heinz

AU - Kaprio, Jaakko

AU - Kardia, Sharon L. R.

AU - Lehtimaki, Terho

AU - Lehrer, Steven F.

AU - Magnusson, Patrik K. E.

AU - Martin, Nicholas G.

AU - McGue, Matt

AU - Metspalu, Andres

AU - Pendleton, Neil

AU - Perola, Markus

AU - Pirastu, Nicola

AU - Pirastu, Mario

AU - Polasek, Ozren

AU - Posthuma, Danielle

AU - Power, Christine

AU - Province, Michael A.

AU - Samani, Nilesh J.

AU - Schlessinger, David

AU - Schmidt, Reinhold

AU - Sorensen, Thorkild I. A.

AU - Spector, Tim D.

AU - Stefansson, Kari

AU - Thorsteinsdottir, Unnur

AU - Thurik, A. Roy

AU - Timpson, Nicholas J.

AU - Tiemeier, Henning

AU - Tung, Joyce Y.

AU - Uitterlinden, Andre G.

AU - Vitart, Veronique

AU - Vollenweider, Peter

AU - Weir, David R.

AU - Wilson, James F.

AU - Wright, Alan F.

AU - Conley, Dalton C.

AU - Krueger, Robert F.

AU - Smith, George Davey

AU - Hofman, Albert

AU - Milaneschi, Yuri

AU - Social Science Genetic Association Consortium

AU - Deleeuw, Christiaan

N1 - With supplementary information.

PY - 2016/5/26

Y1 - 2016/5/26

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 - https://pure.uva.nl/ws/files/62735340/41586_2016_BFnature17671_MOESM48_ESM.pdf

UR - https://pure.uva.nl/ws/files/62735342/41586_2016_BFnature17671_MOESM49_ESM.xlsx

UR - https://pure.uva.nl/ws/files/62735344/41586_2016_BFnature17671_MOESM45_ESM.ppt

UR - https://pure.uva.nl/ws/files/62735346/41586_2016_BFnature17671_MOESM46_ESM.ppt

UR - https://pure.uva.nl/ws/files/62735348/41586_2016_BFnature17671_MOESM47_ESM.ppt

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

U2 - https://doi.org/10.1038/nature17671

DO - https://doi.org/10.1038/nature17671

M3 - Article

C2 - 27225129

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

Abstract

Cohort Studies

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