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

Rietveld CA, Conley D, Eriksson N, Esko T, Medland SE, Vinkhuyzen AA, Yang J, Boardman JD, Chabris CF, Dawes CT, Domingue BW, Hinds DA, Johannesson M, Kiefer AK, Laibson D, Magnusson PK, Mountain JL, Oskarsson S, Rostapshova O, Teumer A, Tung JY, Visscher PM, Benjamin DJ, Cesarini D, Koellinger PD, Social Science Genetics Association Consortium

Psychol Sci 25 (11) 1975-1986 [2014-11-00; online 2014-10-06]

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.

NGI Uppsala (SNP&SEQ Technology Platform) [Service]

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PubMed 25287667

DOI 10.1177/0956797614545132

Crossref 10.1177/0956797614545132

mid NIHMS611855

0956797614545132

pmc PMC4375246