“Replicability and Robustness of Genome-Wide-Association Studies for Behavioral Traits”, 2014 (; backlinks; similar):
A recent genome-wide-association study [ et al 2013] of educational attainment identified 3 single-nucleotide polymorphisms (SNPs) whose associations, despite their small effect sizes (each R2 ≈ 0.02%), reached genome-wide statistical-significance (p < 5 × 10−8) in a large discovery sample and were replicated in an independent sample (p < 0.05). The study also reported associations between educational attainment & indices of SNPs called “polygenic scores”.
In 3 studies, we evaluated the robustness of these findings: Study 1 showed that the associations with all 3 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 population 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.