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

23Andme Research Team, A. Abdellaoui, Wouter J Peyrot, J.J. Hottenga, A.A.E. Vinkhuyzen, Gonneke Willemsen, D.I. Boomsma, Cornelia M van Duijn, Brenda Penninx, Danielle Posthuma, André G Uitterlinden

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
Number of pages10
JournalNature Genetics
Volume50
Issue number8
DOIs
Publication statusPublished - Aug 2018

Fingerprint

Genome-Wide Association Study
Genetic Association Studies
Single Nucleotide Polymorphism
Genome
Phenotype
Neurons
Chromosomes, Human, Pair 10
X Chromosome
Joints
Communication
Brain
Research
Genes

Cite this

23Andme Research Team ; Abdellaoui, A. ; Peyrot, Wouter J ; Hottenga, J.J. ; Vinkhuyzen, A.A.E. ; Willemsen, Gonneke ; Boomsma, D.I. ; van Duijn, Cornelia M ; Penninx, Brenda ; Posthuma, Danielle ; Uitterlinden, André G. / 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.
@article{15efca121efc4e9f8dde4a95180cefda,
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 {23Andme Research Team} 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 Lehrer, {Steven F} and Koellinger, {Philipp D} and A. Abdellaoui and Peyrot, {Wouter J} and J.J. Hottenga and A.A.E. Vinkhuyzen and Gonneke Willemsen and D.I. Boomsma and {van Duijn}, {Cornelia M} and Brenda Penninx and Danielle Posthuma and Uitterlinden, {Andr{\'e} G}",
year = "2018",
month = "8",
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; Abdellaoui, A.; Peyrot, Wouter J; Hottenga, J.J.; Vinkhuyzen, A.A.E.; Willemsen, Gonneke; Boomsma, D.I.; van Duijn, Cornelia M; Penninx, Brenda; Posthuma, Danielle; Uitterlinden, André G.

In: Nature Genetics, Vol. 50, No. 8, 08.2018, 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 - 23Andme Research Team

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 - Lehrer, Steven F

AU - Koellinger, Philipp D

AU - Abdellaoui, A.

AU - Peyrot, Wouter J

AU - Hottenga, J.J.

AU - Vinkhuyzen, A.A.E.

AU - Willemsen, Gonneke

AU - Boomsma, D.I.

AU - van Duijn, Cornelia M

AU - Penninx, Brenda

AU - Posthuma, Danielle

AU - Uitterlinden, André G

PY - 2018/8

Y1 - 2018/8

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.

UR - http://www.scopus.com/inward/record.url?scp=85050543338&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85050543338&partnerID=8YFLogxK

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 -