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

doi: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, 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

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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 language	English
Pages (from-to)	1112-1121
Number of pages	10
Journal	Nature Genetics
Volume	50
Issue number	8
DOIs	https://doi.org/10.1038/s41588-018-0147-3
Publication status	Published - Aug 2018

Funding

This research was carried out under the auspices of the Social Science Genetic Association Consortium (SSGAC). The research has also been conducted using the UK Biobank Resource under application numbers 11425 and 12512. We acknowledge the Swedish Twin Registry for access to data. The Swedish Twin Registry is managed by the Karolinska Institutet and receives funding through the Swedish Research Council under the grant number 2017-00641. This study was supported by funding from the Ragnar Söderberg Foundation (E9/11, E42/15), 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, The Open Philanthropy Project (2016-152872), and the NIA/NIH through grants P01-AG005842, P01-AG005842-20S2, P30-AG012810 and T32-AG000186-23 to N.B.E.R. and R01-AG042568 to U.S.C. A full list of acknowledgments is provided in the Supplementary Note.

Funders	Funder number
Pershing Square Fund	2016-152872
Ragnar Söderberg Foundation	E42/15, 421-2013-1061, E9/11
National Institutes of Health	P30-AG012810, R01-AG042568, T32-AG000186-23
National Institute on Aging	P01AG005842
Jan Wallanders och Tom Hedelius Stiftelse samt Tore Browaldhs Stiftelse
European Research Council	647648 EdGe
Karolinska Institutet
Vetenskapsrådet	2017-00641

Cohort Studies

Netherlands Twin Register (NTR)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individualsFinal published version, 2.58 MBLicence: Article 25fa Dutch Copyright Act

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23Andme Research Team, Abdellaoui, A., Peyrot, W. J., Hottenga, J. J., Vinkhuyzen, A. A. E., Willemsen, G., Boomsma, D. I., van Duijn, C. M., Penninx, B., Posthuma, D., & Uitterlinden, A. G. (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

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23Andme Research Team, Abdellaoui, A, Peyrot, WJ, Hottenga, JJ, Vinkhuyzen, AAE, Willemsen, G , Boomsma, DI, van Duijn, CM, Penninx, B, Posthuma, D & Uitterlinden, AG 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

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

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Cohort Studies

UN SDGs

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