Replicability and Robustness of Genome-Wide-Association Studies for Behavioral Traits

• Published in: Psychological science 2014-11, Vol.25 (11), p.1975-1986
• Main 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.
• Format: Article
• Language: English
• Subjects: Achievement; Associations; Behavior; Biological and medical sciences; Candidates; Correlation analysis; Discovery; Educational attainment; Educational psychology; Educational Status; Fundamental and applied biological sciences. Psychology; Genome-Wide Association Study - methods; Genome-Wide Association Study - statistics & numerical data; Genomes; Genomics; Genotype; Humans; Identification; Independent sample; Level of education; Massachusetts; Personality traits; Polymorphism; Polymorphism, Single Nucleotide - genetics; Principal Component Analysis; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Pupil and student. Academic achievement and failure; Queensland; Registries; Regression analysis; Reproducibility of Results; Robustness; Social stratification; Stratification
• ISSN: 0956-7976; 1467-9280; 1467-9280
• DOI: 10.1177/0956797614545132

A recent genome-wide-association study of educational attainment identified three single-nucleotide polymorphisms (SNPs) whose associations, despite their small effect sizes (each R² ≈ 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 (R² ≈ 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.