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 Nordgren Timshel; Ronald de Vlaming; Abdel Abdellaoui; Tarun Veer Singh 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; Klaus Bønnelykke; Johannes Waage; Hans Bisgaard; Thorkild I A Sørensen; LifeLines Cohort Study

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 Nordgren Timshel, Ronald de Vlaming, Abdel Abdellaoui, Tarun Veer Singh 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, Klaus Bønnelykke, Johannes Waage, Hans Bisgaard, Thorkild I A Sørensen, LifeLines Cohort Study

Department of Clinical Medicine

530 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
Journal	Nature
Volume	533
Issue number	7604
Pages (from-to)	539-42
Number of pages	4
ISSN	0028-0836
DOIs	https://doi.org/10.1038/nature17671
Publication status	Published - 11 May 2016

Keywords

Alzheimer Disease
Bipolar Disorder
Brain
Cognition
Computational Biology
Educational Status
Fetus
Gene Expression Regulation
Gene-Environment Interaction
Genome-Wide Association Study
Great Britain
Humans
Molecular Sequence Annotation
Polymorphism, Single Nucleotide
Schizophrenia
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

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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. N., de Vlaming, R., Abdellaoui, A., Ahluwalia, T. V. S., Bacelis, J., Baumbach, C., ... LifeLines Cohort Study (2016). Genome-wide association study identifies 74 loci associated with educational attainment. Nature, 533(7604), 539-42. https://doi.org/10.1038/nature17671

Okbay, A, Beauchamp, JP, Fontana, MA, Lee, JJ, Pers, TH, Rietveld, CA, Turley, P, Chen, G-B, Emilsson, V, Meddens, SFW, Oskarsson, S, Pickrell, JK, Thom, K, Timshel, PN, de Vlaming, R, Abdellaoui, A, Ahluwalia, TVS, 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, K-O, Liu, T, Mangino, M, Marten, J, Mihailov, E, Miller, MB, Bønnelykke, K, Waage, J, Bisgaard, H, Sørensen, TIA & LifeLines Cohort Study 2016, 'Genome-wide association study identifies 74 loci associated with educational attainment', Nature, vol. 533, no. 7604, pp. 539-42. https://doi.org/10.1038/nature17671

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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.",

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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 Guo-Bo Chen and Valur Emilsson and Meddens, {S Fleur W} and Sven Oskarsson and Pickrell, {Joseph K} and Kevin Thom and Timshel, {Pascal Nordgren} and {de Vlaming}, Ronald and Abdel Abdellaoui and Ahluwalia, {Tarun Veer Singh} 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 Karl-Oskar Lindgren and Tian Liu and Massimo Mangino and Jonathan Marten and Evelin Mihailov and Miller, {Michael B} and Klaus B{\o}nnelykke and Johannes Waage and Hans Bisgaard and S{\o}rensen, {Thorkild I A} and {LifeLines Cohort Study}",

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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 Nordgren

AU - de Vlaming, Ronald

AU - Abdellaoui, Abdel

AU - Ahluwalia, Tarun Veer Singh

AU - Bacelis, Jonas

AU - Baumbach, Clemens

AU - Bjornsdottir, Gyda

AU - Brandsma, Johannes H

AU - Pina Concas, Maria

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 - deLeeuw, 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 - Bønnelykke, Klaus

AU - Waage, Johannes

AU - Bisgaard, Hans

AU - Sørensen, Thorkild I A

AU - LifeLines Cohort Study

PY - 2016/5/11

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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.

KW - Alzheimer Disease

KW - Bipolar Disorder

KW - Brain

KW - Cognition

KW - Computational Biology

KW - Educational Status

KW - Fetus

KW - Gene Expression Regulation

KW - Gene-Environment Interaction

KW - Genome-Wide Association Study

KW - Great Britain

KW - Humans

KW - Molecular Sequence Annotation

KW - Polymorphism, Single Nucleotide

KW - Schizophrenia

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/nature17671

DO - 10.1038/nature17671

M3 - Letter

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

Keywords

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