Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals

23andMe Research Team, James J. Lee, Robbee Wedow, Aysu Okbay, Edward Kong, Omeed Maghzian, Meghan Zacher, Tuan Anh Nguyen-Viet, Peter Bowers, Julia Sidorenko, Richard Karlsson Linnér, Mark Alan Fontana, Tushar Kundu, Chanwook Lee, Hui Li, Ruoxi Li, Rebecca Royer, Pascal N. Timshel, Raymond K Walters, Emily A. Willoughby & 58 others Loïc Yengo, Maris Alver, Yanchun Bao, David W. Clark, Felix R. Day, Nicholas A. Furlotte, Peter K. Joshi, Kathryn E. Kemper, Aaron Kleinman, Claudia Langenberg, Reedik Mägi, Joey W. Trampush, Shefali Setia Verma, Yang Wu, Max Lam, Jing Hua Zhao, Zhili Zheng, Jason D. Boardman, Harry Campbell, Jeremy Freese, Kathleen Mullan Harris, Caroline Hayward, Pamela Herd, Meena Kumari, Todd Lencz, Jian'an Luan, Anil K. Malhotra, Andres Metspalu, Lili Milani, Ken K. Ong, Blair H Smith, John R. B. Perry, David J. Porteous, Marylyn D. Ritchie, Melissa C. Smart, Joyce Y. Tung, Nicholas J. Wareham, James F. Wilson, Jonathan P. Beauchamp, Dalton Conley, Tõnu Esko, Steven F. Lehrer, Patrik K. E. Magnusson, Sven Oskarsson, Tune H. Pers, Matthew R. Robinson, Kevin Thom, Chelsea Watson, Christopher F. Chabris, Michelle N. Meyer, David Laibson, Jian Yang, Magnus Johannesson, Philipp D. Koellinger, Patrick Turley, Peter M. Visscher, Daniel J. Benjamin, David Cesarini

Research output: Contribution to journalArticle

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Abstract

Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.

Original languageEnglish
Pages (from-to)1112-1121
Number of pages10
JournalNature Genetics
Volume50
Issue number8
DOIs
Publication statusPublished - 23 Jul 2018

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Genome-Wide Association Study
Genetic Association Studies
Single Nucleotide Polymorphism
Genome
Phenotype
Neurons
X Chromosome
Joints
Communication
Brain
Research
Genes

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23andMe Research Team, Lee, J. J., Wedow, R., Okbay, A., Kong, E., Maghzian, O., ... Cesarini, D. (2018). Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals. Nature Genetics, 50(8), 1112-1121. https://doi.org/10.1038/s41588-018-0147-3
23andMe Research Team ; Lee, James J. ; Wedow, Robbee ; Okbay, Aysu ; Kong, Edward ; Maghzian, Omeed ; Zacher, Meghan ; Nguyen-Viet, Tuan Anh ; Bowers, Peter ; Sidorenko, Julia ; Karlsson Linnér, Richard ; Fontana, Mark Alan ; Kundu, Tushar ; Lee, Chanwook ; Li, Hui ; Li, Ruoxi ; Royer, Rebecca ; Timshel, Pascal N. ; Walters, Raymond K ; Willoughby, Emily A. ; Yengo, Loïc ; Alver, Maris ; Bao, Yanchun ; Clark, David W. ; Day, Felix R. ; Furlotte, Nicholas A. ; Joshi, Peter K. ; Kemper, Kathryn E. ; Kleinman, Aaron ; Langenberg, Claudia ; Mägi, Reedik ; Trampush, Joey W. ; Verma, Shefali Setia ; Wu, Yang ; Lam, Max ; Zhao, Jing Hua ; Zheng, Zhili ; Boardman, Jason D. ; Campbell, Harry ; Freese, Jeremy ; Harris, Kathleen Mullan ; Hayward, Caroline ; Herd, Pamela ; Kumari, Meena ; Lencz, Todd ; Luan, Jian'an ; Malhotra, Anil K. ; Metspalu, Andres ; Milani, Lili ; Ong, Ken K. ; Smith, Blair H ; Perry, John R. B. ; Porteous, David J. ; Ritchie, Marylyn D. ; Smart, Melissa C. ; Tung, Joyce Y. ; Wareham, Nicholas J. ; Wilson, James F. ; Beauchamp, Jonathan P. ; Conley, Dalton ; Esko, Tõnu ; Lehrer, Steven F. ; Magnusson, Patrik K. E. ; Oskarsson, Sven ; Pers, Tune H. ; Robinson, Matthew R. ; Thom, Kevin ; Watson, Chelsea ; Chabris, Christopher F. ; Meyer, Michelle N. ; Laibson, David ; Yang, Jian ; Johannesson, Magnus ; Koellinger, Philipp D. ; Turley, Patrick ; Visscher, Peter M. ; Benjamin, Daniel J. ; Cesarini, David. / Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals. In: Nature Genetics. 2018 ; Vol. 50, No. 8. pp. 1112-1121.
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title = "Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals",
abstract = "Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3{\%} in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13{\%} of the variance in educational attainment and 7-10{\%} of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.",
author = "{23andMe Research Team} and Lee, {James J.} and Robbee Wedow and Aysu Okbay and Edward Kong and Omeed Maghzian and Meghan Zacher and Nguyen-Viet, {Tuan Anh} and Peter Bowers and Julia Sidorenko and {Karlsson Linn{\'e}r}, Richard and Fontana, {Mark Alan} and Tushar Kundu and Chanwook Lee and Hui Li and Ruoxi Li and Rebecca Royer and Timshel, {Pascal N.} and Walters, {Raymond K} and Willoughby, {Emily A.} and Lo{\"i}c Yengo and Maris Alver and Yanchun Bao and Clark, {David W.} and Day, {Felix R.} and Furlotte, {Nicholas A.} and Joshi, {Peter K.} and Kemper, {Kathryn E.} and Aaron Kleinman and Claudia Langenberg and Reedik M{\"a}gi and Trampush, {Joey W.} and Verma, {Shefali Setia} and Yang Wu and Max Lam and Zhao, {Jing Hua} and Zhili Zheng and Boardman, {Jason D.} and Harry Campbell and Jeremy Freese and Harris, {Kathleen Mullan} and Caroline Hayward and Pamela Herd and Meena Kumari and Todd Lencz and Jian'an Luan and Malhotra, {Anil K.} and Andres Metspalu and Lili Milani and Ong, {Ken K.} and Smith, {Blair H} and Perry, {John R. B.} and Porteous, {David J.} and Ritchie, {Marylyn D.} and Smart, {Melissa C.} and Tung, {Joyce Y.} and Wareham, {Nicholas J.} and Wilson, {James F.} and Beauchamp, {Jonathan P.} and Dalton Conley and T{\~o}nu Esko and Lehrer, {Steven F.} and Magnusson, {Patrik K. E.} and Sven Oskarsson and Pers, {Tune H.} and Robinson, {Matthew R.} and Kevin Thom and Chelsea Watson and Chabris, {Christopher F.} and Meyer, {Michelle N.} and David Laibson and Jian Yang and Magnus Johannesson and Koellinger, {Philipp D.} and Patrick Turley and Visscher, {Peter M.} and Benjamin, {Daniel J.} and David Cesarini",
note = "This study was supported by funding from the Ragnar S{\"o}derberg Foundation (E9/11, E24/15), 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. A full list of acknowledgments is provided in the Supplementary Note.",
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23andMe Research Team, Lee, JJ, Wedow, R, Okbay, A, Kong, E, Maghzian, O, Zacher, M, Nguyen-Viet, TA, Bowers, P, Sidorenko, J, Karlsson Linnér, R, Fontana, MA, Kundu, T, Lee, C, Li, H, Li, R, Royer, R, Timshel, PN, Walters, RK, Willoughby, EA, Yengo, L, Alver, M, Bao, Y, Clark, DW, Day, FR, Furlotte, NA, Joshi, PK, Kemper, KE, Kleinman, A, Langenberg, C, Mägi, R, Trampush, JW, Verma, SS, Wu, Y, Lam, M, Zhao, JH, Zheng, Z, Boardman, JD, Campbell, H, Freese, J, Harris, KM, Hayward, C, Herd, P, Kumari, M, Lencz, T, Luan, J, Malhotra, AK, Metspalu, A, Milani, L, Ong, KK, Smith, BH, Perry, JRB, Porteous, DJ, Ritchie, MD, Smart, MC, Tung, JY, Wareham, NJ, Wilson, JF, Beauchamp, JP, Conley, D, Esko, T, Lehrer, SF, Magnusson, PKE, Oskarsson, S, Pers, TH, Robinson, MR, Thom, K, Watson, C, Chabris, CF, Meyer, MN, Laibson, D, Yang, J, Johannesson, M, Koellinger, PD, Turley, P, Visscher, PM, Benjamin, DJ & Cesarini, D 2018, 'Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals', Nature Genetics, vol. 50, no. 8, pp. 1112-1121. https://doi.org/10.1038/s41588-018-0147-3

Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals. / 23andMe Research Team; Lee, James J.; Wedow, Robbee; Okbay, Aysu; Kong, Edward; Maghzian, Omeed; Zacher, Meghan; Nguyen-Viet, Tuan Anh; Bowers, Peter; Sidorenko, Julia; Karlsson Linnér, Richard; Fontana, Mark Alan; Kundu, Tushar; Lee, Chanwook; Li, Hui; Li, Ruoxi; Royer, Rebecca; Timshel, Pascal N.; Walters, Raymond K; Willoughby, Emily A.; Yengo, Loïc; Alver, Maris; Bao, Yanchun; Clark, David W.; Day, Felix R.; Furlotte, Nicholas A.; Joshi, Peter K.; Kemper, Kathryn E.; Kleinman, Aaron; Langenberg, Claudia; Mägi, Reedik; Trampush, Joey W.; Verma, Shefali Setia; Wu, Yang; Lam, Max; Zhao, Jing Hua; Zheng, Zhili; Boardman, Jason D.; Campbell, Harry; Freese, Jeremy; Harris, Kathleen Mullan; Hayward, Caroline; Herd, Pamela; Kumari, Meena; Lencz, Todd; Luan, Jian'an; Malhotra, Anil K.; Metspalu, Andres; Milani, Lili; Ong, Ken K.; Smith, Blair H; Perry, John R. B.; Porteous, David J.; Ritchie, Marylyn D.; Smart, Melissa C.; Tung, Joyce Y.; Wareham, Nicholas J.; Wilson, James F.; Beauchamp, Jonathan P.; Conley, Dalton; Esko, Tõnu; Lehrer, Steven F.; Magnusson, Patrik K. E.; Oskarsson, Sven; Pers, Tune H.; Robinson, Matthew R.; Thom, Kevin; Watson, Chelsea; Chabris, Christopher F.; Meyer, Michelle N.; Laibson, David; Yang, Jian; Johannesson, Magnus; Koellinger, Philipp D.; Turley, Patrick; Visscher, Peter M. (Lead / Corresponding author); Benjamin, Daniel J. (Lead / Corresponding author); Cesarini, David.

In: Nature Genetics, Vol. 50, No. 8, 23.07.2018, p. 1112-1121.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals

AU - 23andMe Research Team

AU - Lee, James J.

AU - Wedow, Robbee

AU - Okbay, Aysu

AU - Kong, Edward

AU - Maghzian, Omeed

AU - Zacher, Meghan

AU - Nguyen-Viet, Tuan Anh

AU - Bowers, Peter

AU - Sidorenko, Julia

AU - Karlsson Linnér, Richard

AU - Fontana, Mark Alan

AU - Kundu, Tushar

AU - Lee, Chanwook

AU - Li, Hui

AU - Li, Ruoxi

AU - Royer, Rebecca

AU - Timshel, Pascal N.

AU - Walters, Raymond K

AU - Willoughby, Emily A.

AU - Yengo, Loïc

AU - Alver, Maris

AU - Bao, Yanchun

AU - Clark, David W.

AU - Day, Felix R.

AU - Furlotte, Nicholas A.

AU - Joshi, Peter K.

AU - Kemper, Kathryn E.

AU - Kleinman, Aaron

AU - Langenberg, Claudia

AU - Mägi, Reedik

AU - Trampush, Joey W.

AU - Verma, Shefali Setia

AU - Wu, Yang

AU - Lam, Max

AU - Zhao, Jing Hua

AU - Zheng, Zhili

AU - Boardman, Jason D.

AU - Campbell, Harry

AU - Freese, Jeremy

AU - Harris, Kathleen Mullan

AU - Hayward, Caroline

AU - Herd, Pamela

AU - Kumari, Meena

AU - Lencz, Todd

AU - Luan, Jian'an

AU - Malhotra, Anil K.

AU - Metspalu, Andres

AU - Milani, Lili

AU - Ong, Ken K.

AU - Smith, Blair H

AU - Perry, John R. B.

AU - Porteous, David J.

AU - Ritchie, Marylyn D.

AU - Smart, Melissa C.

AU - Tung, Joyce Y.

AU - Wareham, Nicholas J.

AU - Wilson, James F.

AU - Beauchamp, Jonathan P.

AU - Conley, Dalton

AU - Esko, Tõnu

AU - Lehrer, Steven F.

AU - Magnusson, Patrik K. E.

AU - Oskarsson, Sven

AU - Pers, Tune H.

AU - Robinson, Matthew R.

AU - Thom, Kevin

AU - Watson, Chelsea

AU - Chabris, Christopher F.

AU - Meyer, Michelle N.

AU - Laibson, David

AU - Yang, Jian

AU - Johannesson, Magnus

AU - Koellinger, Philipp D.

AU - Turley, Patrick

AU - Visscher, Peter M.

AU - Benjamin, Daniel J.

AU - Cesarini, David

N1 - This study was supported by funding from the Ragnar Söderberg Foundation (E9/11, E24/15), 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. A full list of acknowledgments is provided in the Supplementary Note.

PY - 2018/7/23

Y1 - 2018/7/23

N2 - Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.

AB - Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.

U2 - 10.1038/s41588-018-0147-3

DO - 10.1038/s41588-018-0147-3

M3 - Article

VL - 50

SP - 1112

EP - 1121

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 8

ER -