title: Replicability and robustness of genome-wide-association studies for behavioral traits.
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.
authors.affiliation: Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Cornelius A
authors.initials: CA
authors.lastname: Rietveld
authors.affiliation: Department of Sociology, New York University.
authors.forename: Dalton
authors.initials: D
authors.lastname: Conley
authors.affiliation: 23andMe, Inc., Mountain View, California.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Eriksson
authors.affiliation: Estonian Genome Center, University of Tartu.
authors.forename: Tõnu
authors.initials: T
authors.lastname: Esko
authors.affiliation: Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Medland
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane.
authors.forename: Anna A E
authors.initials: AA
authors.lastname: Vinkhuyzen
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Institute of Behavioral Science, University of Colorado, Boulder Department of Sociology, University of Colorado, Denver.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Boardman
authors.affiliation: Department of Psychology, Union College.
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Chabris
authors.affiliation: Wilf Family Department of Politics, New York University.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Dawes
authors.affiliation: Institute of Behavioral Science, University of Colorado, Boulder.
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Domingue
authors.affiliation: 23andMe, Inc., Mountain View, California.
authors.forename: David A
authors.initials: DA
authors.lastname: Hinds
authors.affiliation: Department of Economics, Stockholm School of Economics.
authors.forename: Magnus
authors.initials: M
authors.lastname: Johannesson
authors.affiliation: 23andMe, Inc., Mountain View, California.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Kiefer
authors.affiliation: Department of Economics, Harvard University.
authors.forename: David
authors.initials: D
authors.lastname: Laibson
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
authors.forename: Patrik K E
authors.initials: PK
authors.lastname: Magnusson
authors.affiliation: 23andMe, Inc., Mountain View, California.
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Mountain
authors.affiliation: Department of Government, Uppsala University.
authors.forename: Sven
authors.initials: S
authors.lastname: Oskarsson
authors.affiliation: Department of Economics, Harvard University.
authors.forename: Olga
authors.initials: O
authors.lastname: Rostapshova
authors.affiliation: Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, Greifswald Medical School.
authors.forename: Alexander
authors.initials: A
authors.lastname: Teumer
authors.affiliation: 23andMe, Inc., Mountain View, California.
authors.forename: Joyce Y
authors.initials: JY
authors.lastname: Tung
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane University of Queensland Diamantina Institute, Princess Alexandra Hospital, The University of Queensland, Brisbane.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Visscher
authors.affiliation: Department of Economics, Cornell University.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Benjamin
authors.affiliation: Center for Experimental Social Science, Department of Economics, New York University Institute for the Interdisciplinary Study of Decision Making, New York University.
authors.forename: David
authors.initials: D
authors.lastname: Cesarini
authors.affiliation: Department 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.
authors.forename: Philipp D
authors.initials: PD
authors.lastname: Koellinger
mesh_terms: D000124:Achievement; D004522:Educational Status; D055106:Genome-Wide Association Study / Q000379:methods* / Q000706:statistics & numerical data*; D005838:Genotype; D006801:Humans; D008404:Massachusetts; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D025341:Principal Component Analysis; D011793:Queensland; D012042:Registries; D015203:Reproducibility of Results
keywords: behavior genetics; educational attainment; genome-wide association study; individual differences; population stratification