Replicability and Robustness of Genome-Wide-Association Studies for Behavioral Traits. (November 2014)

• Record Type: Journal Article
• Authors: Rietveld, Cornelius A.; Conley, Dalton; Eriksson, Nicholas; Esko, Tõnu; 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.
• Other Names: Eriksson N. non-byline-author.; Hinds D. A. non-byline-author.; Kiefer A. K. non-byline-author.; Mountain J. L. non-byline-author.; Tung J. Y. non-byline-author.; Medland S. E. non-byline-author.; Vinkhuyzen A. A. E. non-byline-author.; Yang J. non-byline-author.; Visscher P. M. non-byline-author.; Conley D. non-byline-author.; Boardman J. D. non-byline-author.; Dawes C. T. non-byline-author.; Domingue B. W. non-byline-author.; Rietveld C. A. non-byline-author.; Benjamin D. J. non-byline-author.; Cesarini D. non-byline-author.; Koellinger P. D. non-byline-author.; Conley D. non-byline-author.; Eriksson N. non-byline-author.; Esko T. non-byline-author.; Chabris C. F. non-byline-author.; Johannesson M. non-byline-author.; Laibson D. non-byline-author.; Magnusson P. K. E. non-byline-author.; Oskarsson S. non-byline-author.; Rostapshova O. non-byline-author.; Teumer A. non-byline-author.; Visscher P. M. non-byline-author.; Benjamin D. J. non-byline-author.; Cesarini D. non-byline-author.; Koellinger P. D. non-byline-author.;
• Is Part Of: Psychological science. Volume 25:Number 11(2014:Nov.)
• Page Start: 1975
• Page End: 1986
• Publication Date: 2014-11
• Subjects: behavior genetics -- educational attainment -- individual differences -- genome-wide association study -- population stratification; Psychology -- Periodicals; 150.5
• DOI: 10.1177/0956797614545132
• Languages: English
• ISSNs: 0956-7976

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.