QIMR Berghofer

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) approximately 0.02%), reached genome-wide significance (p < 5 x 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) approximately 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 Rietveld, Cornelius A.; Conley, Dalton; Eriksson, Nicholas; Esko, Tonu; Medland, Sarah E.; Vinkhuyzen, Anna A. E.; Yang, Jian; Boardman, Jason D.; Chabris, Christopher F.; Dawes, Christopher T.; Domingue, Benjamin W.; Hinds, David A.; Johannesson, Magnus; Kiefer, Amy K.; Laibson, David; Magnusson, Patrik K. E.; Mountain, Joanna L.; Oskarsson, Sven; Rostapshova, Olga; Teumer, Alexander; Tung, Joyce Y.; Visscher, Peter M.; Benjamin, Daniel J.; Cesarini, David; Koellinger, Philipp D.
Journal Psychological Science
Pages 1975-86
Volume 25
Date 1/11/2014
Grant ID
Funding Body
URL http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1177/0956797614545132