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

Cornelius A. Rietveld, Dalton Conley, Nicholas Eriksson, Tõnu Esko, Sarah E. Medland, Anna A.E. Vinkhuyzen, Jian Yang, Jason D. Boardman, Christopher F. Chabris, Christopher T. Dawes, Benjamin W. Domingue, David A. Hinds, Magnus Johannesson, Amy K. Kiefer, David Laibson, Patrik K.E. Magnusson, Joanna L. Mountain, Sven Oskarsson, Olga Rostapshova, Alexander TeumerJoyce Y. Tung, Peter M. Visscher, Daniel J. Benjamin, David Cesarini, Philipp D. Koellinger

Research output: Contribution to journalArticle

53 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1975-1986
Number of pages12
JournalPsychological Science
Volume25
Issue number11
DOIs
StatePublished - Nov 20 2014

All Science Journal Classification (ASJC) codes

  • Psychology(all)

Keywords

  • behavior genetics
  • educational attainment
  • genome-wide association study
  • individual differences
  • population stratification

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    Rietveld, C. A., Conley, D., Eriksson, N., Esko, T., Medland, S. E., Vinkhuyzen, A. A. E., Yang, J., Boardman, J. D., Chabris, C. F., Dawes, C. T., Domingue, B. W., Hinds, D. A., Johannesson, M., Kiefer, A. K., Laibson, D., Magnusson, P. K. E., Mountain, J. L., Oskarsson, S., Rostapshova, O., ... Koellinger, P. D. (2014). Replicability and Robustness of Genome-Wide-Association Studies for Behavioral Traits. Psychological Science, 25(11), 1975-1986. https://doi.org/10.1177/0956797614545132