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 · 22 23andMe (United States) · 23 QIMR Berghofer Medical Research Institute · 24 The University of Queensland · 25 New York University · 26 University of Colorado Boulder · 27 University of Colorado Denver · 28 University of Colorado System · 29 Erasmus MC · 30 Erasmus University Rotterdam · 31 Cornell University · 32 University of Amsterdam · 33 University of Tartu · 34 Union College · 35 Stockholm School of Economics · 36 Harvard University · 37 Karolinska Institutet · 38 Uppsala University · 39 Harvard University Press
open access
Abstract
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.