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 & 31 others 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, Lynne J Hocking, LifeLines Cohort Study

Research output: Contribution to journalLetter

351 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 languageEnglish
Pages (from-to)539-542
Number of pages4
JournalNature
Volume533
Issue number7604
Early online date11 May 2016
DOIs
Publication statusPublished - 26 May 2016

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Genome-Wide Association Study
Phenotype
Proxy
Cognition
Single Nucleotide Polymorphism
Genome
Gene Expression
Brain
Genes

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

Genome-wide association study identifies 74 loci associated with educational attainment. / Okbay, Aysu; Beauchamp, Jonathan P; Fontana, Mark Alan; Lee, James J; Pers, Tune H; Rietveld, Cornelius A; Turley, Patrick; Chen, Guo-Bo; Emilsson, Valur; Meddens, S Fleur W; Oskarsson, Sven; Pickrell, Joseph K; Thom, Kevin; Timshel, Pascal; de Vlaming, Ronald; Abdellaoui, Abdel; Ahluwalia, Tarunveer S; Bacelis, Jonas; Baumbach, Clemens; Bjornsdottir, Gyda; Brandsma, Johannes H; Pina Concas, Maria; Derringer, Jaime; Furlotte, Nicholas A; Galesloot, Tessel E; Girotto, Giorgia; Gupta, Richa; Hall, Leanne M; Harris, Sarah E; Hofer, Edith; Horikoshi, Momoko; Huffman, Jennifer E; Kaasik, Kadri; Kalafati, Ioanna P; Karlsson, Robert; Kong, Augustine; Lahti, Jari; van der Lee, Sven J; deLeeuw, Christiaan; Lind, Penelope A; Lindgren, Karl-Oskar; Liu, Tian; Mangino, Massimo; Marten, Jonathan; Mihailov, Evelin; Miller, Michael B; van der Most, Peter J; Oldmeadow, Christopher; Payton, Antony; Hocking, Lynne J; LifeLines Cohort Study.

In: Nature, Vol. 533, No. 7604, 26.05.2016, p. 539-542.

Research output: Contribution to journalLetter

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, 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, K-O, Liu, T, Mangino, M, Marten, J, Mihailov, E, Miller, MB, van der Most, PJ, Oldmeadow, C, Payton, A, Hocking, LJ & LifeLines Cohort Study 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
Okbay A, Beauchamp JP, Fontana MA, Lee JJ, Pers TH, Rietveld CA et al. Genome-wide association study identifies 74 loci associated with educational attainment. Nature. 2016 May 26;533(7604):539-542. https://doi.org/10.1038/nature17671
Okbay, Aysu ; Beauchamp, Jonathan P ; Fontana, Mark Alan ; Lee, James J ; Pers, Tune H ; Rietveld, Cornelius A ; Turley, Patrick ; Chen, Guo-Bo ; Emilsson, Valur ; Meddens, S Fleur W ; Oskarsson, Sven ; Pickrell, Joseph K ; Thom, Kevin ; Timshel, Pascal ; de Vlaming, Ronald ; Abdellaoui, Abdel ; Ahluwalia, Tarunveer S ; Bacelis, Jonas ; Baumbach, Clemens ; Bjornsdottir, Gyda ; Brandsma, Johannes H ; Pina Concas, Maria ; Derringer, Jaime ; Furlotte, Nicholas A ; Galesloot, Tessel E ; Girotto, Giorgia ; Gupta, Richa ; Hall, Leanne M ; Harris, Sarah E ; Hofer, Edith ; Horikoshi, Momoko ; Huffman, Jennifer E ; Kaasik, Kadri ; Kalafati, Ioanna P ; Karlsson, Robert ; Kong, Augustine ; Lahti, Jari ; van der Lee, Sven J ; deLeeuw, Christiaan ; Lind, Penelope A ; Lindgren, Karl-Oskar ; Liu, Tian ; Mangino, Massimo ; Marten, Jonathan ; Mihailov, Evelin ; Miller, Michael B ; van der Most, Peter J ; Oldmeadow, Christopher ; Payton, Antony ; Hocking, Lynne J ; LifeLines Cohort Study. / Genome-wide association study identifies 74 loci associated with educational attainment. In: Nature. 2016 ; Vol. 533, No. 7604. pp. 539-542.
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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 Guo-Bo Chen 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 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 Hocking, {Lynne J} and {LifeLines Cohort Study}",
note = "This research was carried out under the auspices of the Social Science Genetic Association Consortium (SSGAC). This research has also been conducted using the UK Biobank Resource. 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. We thank S. Cunningham, N. Galla and J. Rashtian for research assistance",
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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

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 - van der Most, Peter J

AU - Oldmeadow, Christopher

AU - Payton, Antony

AU - Hocking, Lynne J

AU - LifeLines Cohort Study

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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.

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DO - 10.1038/nature17671

M3 - Letter

VL - 533

SP - 539

EP - 542

JO - Nature

JF - Nature

SN - 0028-0836

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