Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

23andMe Inc., Social Science Genetic Association Consortium, Lifelines Cohort Study

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Abstract

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12–16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI’s magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57.

Original languageEnglish
Pages (from-to)437-449
Number of pages13
JournalNature Genetics
Volume54
Issue number4
DOIs
Publication statusPublished - 31 Mar 2022

Bibliographical note

Acknowledgements:
We thank E.M. Tucker-Drob for helpful comments and J. Zeng for help with the SBayesR
software. This research was carried out under the auspices of the Social Science Genetic
Association Consortium. The analyses reported in the paper fall under National
Bureau of Economic Research institutional review board protocols 19_434, 19_465 and
20_041. This paper uses cohort-level data from Okbay et al.62, and information about
studies participating in that study can be found in the Additional Acknowledgements
Supplementary section of that paper. Per Social Science Genetic Association Consortium
policy, we acknowledge the authors of that paper, listed below, as collaborators. 23andMe
research participants provided informed consent and participated in the research
online, under a protocol approved by the external Association for the Accreditation of
Human Research Protection Programs-accredited institutional review board, Ethical &
Independent Review Services. Participants were included in the analysis on the basis of
consent status as checked at the time data analyses were initiated. We would like to thank
the research participants and employees of 23andMe for making this work possible. We
gratefully acknowledge the contributions of members of 23andMe’s Research Team, whose
names are listed below. The research has also been conducted using the UKB Resource
under application numbers 11425 and 12505. Informed consent was obtained from
UKB subjects. Ethical approval for the GS: Scottish Family Health Study was obtained
from the Tayside Committee on Medical Research Ethics (on behalf of the National
Health Service). H.J, M.B., D. Cesarini and P.T. were supported by the Ragnar Söderberg
Foundation (E42/15 to D. Cesarini); A.O. and P.K. by the European Research Council
(consolidator grant 647648 EdGe to P.K.); H.J., M.B., S.M.N., T.G., C.W., J.J., M.N.M.,
D. Cesarini, P.T., J.P.B., D.J.B. and A.I.Y. by Open Philanthropy (grant 010623-00001 to
D.J.B.); R.A. and S.O. by Riksbankens Jubileumsfond (grant P18-0782:1 to S.O.); N.W.,
G.G., C.W., L.Y. and D.J.B. by the National Institute on Aging (NIA)/National Institutes
of Health (NIH) (grants R24-AG065184 and R01-AG042568 to D.J.B.); D.J.B. by the NIA/
NIH (grant R56-AG058726 to T. Galama); P.T. by the NIA/National Institute on Mental
Health (grants R01-MH101244-02 and U01-MH109539-02 to B. Neale); J.S. and P.M.V. by
the Australian Research Council (grant FL180100072 to P.M.V.); and Y.W., L.Y. and P.M.V.
by the National Health and Medical Research Council (grant GNT113400 to P.M.V.).
The study was also supported by Netherlands Organisation for Scientific Research VENI
(grant 016.Veni.198.058 to A.O.); the F.G. Meade Scholarship and UQ Research Training
Scholarship from the University of Queensland Senate (Y.W.); the Swedish Research
Council (grant 2019-00244 to S.O.); an MRC University Unit Programme Grant
(MC_UU_00007/10, QTL in Health and Disease, to C.H.); the Swedish Research Council
(grant 421-2013-1061 to M.J.); Pershing Square Fund of the Foundations of Human
Behavior (D.L.); the Li Ka Shing Foundation (A.K.); the Australian Research Council
(grant DE200100425 to L.Y.); the NIA/NIH (grant K99-AG062787-01 to P.T.); the
Government of Canada through Genome Canada and the Ontario Genomics Institute
(grant OGI-152 to J.P.B.); the Social Sciences and Humanities Research Council of
Canada (J.P.B.); and the Australian Research Council (P.M.V.).

Publisher Copyright: © 2022, The Author(s).

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