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.B. 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.P. 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. de Leeuw; P.A. Lind; K.O. Lindgren; T. Liu; M. Mangino; J. Marten; E. Mihailov; M.B. Miller; P.J. van der Most; C. Oldmeadow; A. Payton; N. Pervjakova; LifeLines Cohort Study; Daniel J Benjamin; Jan Staessen

doi:10.1038/nature17671

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.B. 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. BjornsdottirJ.H. Brandsma, M.P. 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. de Leeuw, P.A. Lind, K.O. Lindgren, T. Liu, M. Mangino, J. Marten, E. Mihailov, M.B. Miller, P.J. van der Most, C. Oldmeadow, A. Payton, N. Pervjakova, LifeLines Cohort Study, Daniel J Benjamin^*, Jan Staessen

^*Corresponding author for this work

Epidemiologie

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

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(1). Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample(1,2) 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	16
Journal	Nature
Volume	533
Issue number	7604
DOIs	https://doi.org/10.1038/nature17671
Publication status	Published - 26 May 2016

Keywords

HERITABILITY
ACHIEVEMENT
IQ

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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., ... Staessen, J. (2016). Genome-wide association study identifies 74 loci associated with educational attainment. Nature, 533(7604), 539-542. https://doi.org/10.1038/nature17671

@article{aa42cfcce25e495d9842c4583e73ef2e,

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(1). Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample(1,2) 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.",

keywords = "HERITABILITY, ACHIEVEMENT, IQ",

author = "A. Okbay and J.P. 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 S.F.W. Meddens and S. Oskarsson and J.K. Pickrell and K. Thom and P. Timshel and \{de Vlaming\}, R. and A. Abdellaoui and T.S. Ahluwalia and J. Bacelis and C. Baumbach and G. Bjornsdottir and J.H. Brandsma and M.P. Concas and J. Derringer and N.A. Furlotte and T.E. Galesloot and G. Girotto and R. Gupta and L.M. Hall and S.E. Harris and E. Hofer and M. Horikoshi and J.E. Huffman and K. Kaasik and I.P. Kalafati and R. Karlsson and A. Kong and J. Lahti and \{van der Lee\}, S.J. and \{de Leeuw\}, C. and P.A. Lind and K.O. Lindgren and T. Liu and M. Mangino and J. Marten and E. Mihailov and M.B. Miller and \{van der Most\}, P.J. and C. Oldmeadow and A. Payton and N. Pervjakova and \{LifeLines Cohort Study\} and Benjamin, \{Daniel J\} and Jan Staessen",

year = "2016",

month = may,

day = "26",

doi = "10.1038/nature17671",

language = "English",

volume = "533",

pages = "539--542",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "7604",

}

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, Concas, MP, 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, de Leeuw, 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, LifeLines Cohort Study, Benjamin, DJ & Staessen, J 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.P.

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 - Meddens, S.F.W.

AU - Oskarsson, S.

AU - Pickrell, J.K.

AU - Thom, K.

AU - Timshel, P.

AU - de Vlaming, R.

AU - Abdellaoui, A.

AU - Ahluwalia, T.S.

AU - Bacelis, J.

AU - Baumbach, C.

AU - Bjornsdottir, G.

AU - Brandsma, J.H.

AU - Concas, M.P.

AU - Derringer, J.

AU - Furlotte, N.A.

AU - Galesloot, T.E.

AU - Girotto, G.

AU - Gupta, R.

AU - Hall, L.M.

AU - Harris, S.E.

AU - Hofer, E.

AU - Horikoshi, M.

AU - Huffman, J.E.

AU - Kaasik, K.

AU - Kalafati, I.P.

AU - Karlsson, R.

AU - Kong, A.

AU - Lahti, J.

AU - van der Lee, S.J.

AU - de Leeuw, C.

AU - Lind, P.A.

AU - Lindgren, K.O.

AU - Liu, T.

AU - Mangino, M.

AU - Marten, J.

AU - Mihailov, E.

AU - Miller, M.B.

AU - van der Most, P.J.

AU - Oldmeadow, C.

AU - Payton, A.

AU - Pervjakova, N.

AU - LifeLines Cohort Study

AU - Benjamin, Daniel J

AU - Staessen, Jan

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(1). Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample(1,2) 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(1). Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample(1,2) 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.

KW - HERITABILITY

KW - ACHIEVEMENT

KW - IQ

U2 - 10.1038/nature17671

DO - 10.1038/nature17671

M3 - Article

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

Keywords

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