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

23andMe Research team

Research output: Contribution to journalArticleAcademicpeer-review

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
JournalNature Genetics
Volume50
Issue number8
DOIs
Publication statusPublished - 2018

Cite this

@article{6a227c1ed1ba4bd6a87efb157b96d6e4,
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 = "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 Michelle Agee and Babak Alipanahi and Adam Auton and Bell, {Robert K.} and Katarzyna Bryc and Elson, {Sarah L.} and Pierre Fontanillas and Hinds, {David A.} and McCreight, {Jennifer C.} and Huber, {Karen E.} and Litterman, {Nadia K.} and McIntyre, {Matthew H.} and Mountain, {Joanna L.} and Noblin, {Elizabeth S.} and Northover, {Carrie A. M.} and Pitts, {Steven J.} and Sathirapongsasuti, {J. Fah} and {van der Lee}, {Sven J.} and Peyrot, {Wouter J.} and Evans, {David M.} and Yusplitri Milaneschi and Eriksson, {Johan G.} and Penninx, {Brenda W. J. H.} and Danielle Posthuma and {van der Lee}, {Sven J.} and Peyrot, {Wouter J.} and Evans, {David M.} and Eriksson, {Johan G.} and Penninx, {Brenda W. J. H.} and Danielle Posthuma and {23andMe Research team}",
year = "2018",
doi = "10.1038/s41588-018-0147-3",
language = "English",
volume = "50",
pages = "1112--1121",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "8",

}

Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals. / 23andMe Research team.

In: Nature Genetics, Vol. 50, No. 8, 2018, p. 1112-1121.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

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

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 - Agee, Michelle

AU - Alipanahi, Babak

AU - Auton, Adam

AU - Bell, Robert K.

AU - Bryc, Katarzyna

AU - Elson, Sarah L.

AU - Fontanillas, Pierre

AU - Hinds, David A.

AU - McCreight, Jennifer C.

AU - Huber, Karen E.

AU - Litterman, Nadia K.

AU - McIntyre, Matthew H.

AU - Mountain, Joanna L.

AU - Noblin, Elizabeth S.

AU - Northover, Carrie A. M.

AU - Pitts, Steven J.

AU - Sathirapongsasuti, J. Fah

AU - van der Lee, Sven J.

AU - Peyrot, Wouter J.

AU - Evans, David M.

AU - Milaneschi, Yusplitri

AU - Eriksson, Johan G.

AU - Penninx, Brenda W. J. H.

AU - Posthuma, Danielle

AU - van der Lee, Sven J.

AU - Peyrot, Wouter J.

AU - Evans, David M.

AU - Eriksson, Johan G.

AU - Penninx, Brenda W. J. H.

AU - Posthuma, Danielle

AU - 23andMe Research team

PY - 2018

Y1 - 2018

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.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/30038396

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 -