Replicability and robustness of genome-wide-association studies for behavioral traits

Psychol Sci. 2014 Nov;25(11):1975-86. doi: 10.1177/0956797614545132. Epub 2014 Oct 6.

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.

Keywords: behavior genetics; educational attainment; genome-wide association study; individual differences; population stratification.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Achievement*
  • Educational Status
  • Genome-Wide Association Study / methods*
  • Genome-Wide Association Study / statistics & numerical data*
  • Genotype
  • Humans
  • Massachusetts
  • Polymorphism, Single Nucleotide / genetics*
  • Principal Component Analysis
  • Queensland
  • Registries
  • Reproducibility of Results