Psychol Sci. 2014 Oct 6. pii: 0956797614545132. [Epub ahead of print]

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

Rietveld CA1, Conley D2, Eriksson N3, Esko T4, Medland SE5, Vinkhuyzen AA6, Yang J6, Boardman JD7, Chabris CF8, Dawes CT9, Domingue BW10, Hinds DA3, Johannesson M11, Kiefer AK3, Laibson D12, Magnusson PK13, Mountain JL3, Oskarsson S14, Rostapshova O12, Teumer A15, Tung JY3, Visscher PM16,Benjamin DJ17, Cesarini D18, Koellinger PD19; the Social Science Genetics Association Consortium; the Social Science Genetics Association Consortium.

Collaborators (31)

Author information

• 1Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
• 2Department of Sociology, New York University.
• 323andMe, Inc., Mountain View, California.
• 4Estonian Genome Center, University of Tartu.
• 5Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
• 6Queensland Brain Institute, The University of Queensland, Brisbane.
• 7Institute of Behavioral Science, University of Colorado, Boulder Department of Sociology, University of Colorado, Denver.
• 8Department of Psychology, Union College.
• 9Wilf Family Department of Politics, New York University.
• 10Institute of Behavioral Science, University of Colorado, Boulder.
• 11Department of Economics, Stockholm School of Economics.
• 12Department of Economics, Harvard University.
• 13Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
• 14Department of Government, Uppsala University.
• 15Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, Greifswald Medical School.
• 16Queensland Brain Institute, The University of Queensland, Brisbane University of Queensland Diamantina Institute, Princess Alexandra Hospital, The University of Queensland, Brisbane.
• 17Department of Economics, Cornell University.
• 18Center for Experimental Social Science, Department of Economics, New York University Institute for the Interdisciplinary Study of Decision Making, New York University.
• 19Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands Faculty of Economics and Business, University of Amsterdam p.d.koellinger@uva.nl.

Abstract

A recent genome-wide-association study of educational attainment identified three single-nucleotide polymorphisms (SNPs) whose associations, despite their small effect sizes (each R2 ≈ 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 (R2 ≈ 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.