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Replicability and Robustness of Genome-Wide-Association Studies for Behavioral Traits

Cornelius A. Rietveld^1,2; Dalton Conley³; Nicholas Eriksson⁴; Tõnu Esko⁵; Sarah E. Medland⁶; Anna A. E. Vinkhuyzen⁷; Jian Yang⁷; Jason D. Boardman^8,9; Christopher F. Chabris¹⁰; Christopher T. Dawes¹¹; Benjamin W. Domingue⁸; David A. Hinds⁴; Magnus Johannesson¹²; Amy K. Kiefer⁴; David Laibson¹³; Patrik K. E. Magnusson¹⁴; Joanna L. Mountain⁴; Sven Oskarsson¹⁵; Olga Rostapshova¹³; Alexander Teumer¹⁶; Joyce Y. Tung⁴; Peter M. Visscher^7,17; Daniel J. Benjamin¹⁸; David Cesarini^19,20; Philipp D. Koellinger^1,2,21; the Social Science Genetics Association Consortium; N. Eriksson; D. A. Hinds; A. K. Kiefer; J. L. Mountain; J. Y. Tung; S. E. Medland; A. A. E. Vinkhuyzen; J. Yang; P. M. Visscher; D. Conley; J. D. Boardman; C. T. Dawes; B. W. Domingue; C. A. Rietveld; D. J. Benjamin; D. Cesarini; P. D. Koellinger; D. Conley; N. Eriksson; T. Esko; C. F. Chabris; M. Johannesson; D. Laibson; P. K. E. Magnusson; S. Oskarsson; O. Rostapshova; A. Teumer; P. M. Visscher; D. J. Benjamin; D. Cesarini; P. D. Koellinger

¹ Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam · ² Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands · ³ Department of Sociology, New York University · ⁴ 23andMe, Inc., Mountain View, California · ⁵ Estonian Genome Center, University of Tartu · ⁶ Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia · ⁷ Queensland Brain Institute, The University of Queensland, Brisbane · ⁸ Institute of Behavioral Science, University of Colorado, Boulder · ⁹ Department of Sociology, University of Colorado, Denver · ¹⁰ Department of Psychology, Union College · ¹¹ Wilf Family Department of Politics, New York University · ¹² Department of Economics, Stockholm School of Economics · ¹³ Department of Economics, Harvard University · ¹⁴ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet · ¹⁵ Department of Government, Uppsala University · ¹⁶ Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, Greifswald Medical School · ¹⁷ University of Queensland Diamantina Institute, Princess Alexandra Hospital, The University of Queensland, Brisbane · ¹⁸ Department of Economics, Cornell University · ¹⁹ Center for Experimental Social Science, Department of Economics, New York University · ²⁰ Institute for the Interdisciplinary Study of Decision Making, New York University · ²¹ Faculty of Economics and Business, University of Amsterdam

A recent genome-wide-association study of educational attainment identified three single-nucleotide polymorphisms (SNPs) whose associations, despite their small effect sizes (each R 2 ≈ 0.02%), reached genome-wide significance ( p < 5 × 10 −8 ) in a large discovery sample and were replicated in an independent sample ( p < .05). The study also reported associations between educational attainment and indices of SNPs called “polygenic scores.” In three studies, we evaluated the robustness of these findings. Study 1 showed that the associations with all three SNPs were replicated in another large ( N = 34,428) independent sample. We also found that the scores remained predictive ( R 2 ≈ 2%) in regressions with stringent controls for stratification (Study 2) and in new within-family analyses (Study 3). Our results show that large and therefore well-powered genome-wide-association studies can identify replicable genetic associations with behavioral traits. The small effect sizes of individual SNPs are likely to be a major contributing factor explaining the striking contrast between our results and the disappointing replication record of most candidate-gene studies.

DOI

10.1177/0956797614545132

Volume

25 (11)

Pages

1975-1986

Language

en

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