Replicability and Robustness of Genome-Wide-Association Studies for Behavioral Traits
Year: 2014
Type: article
Study design: Observational Study
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.
Source: Psychological Science
Authors: Cornelius A. Rietveld, Dalton Conley, Nicholas Eriksson, Tõnu Esko, Sarah E. Medland, Anna A. E. Vinkhuyzen, Jian Yang, Jason D. Boardman, Christopher F. Chabris, Christopher T. Dawes, Benjamin W. Domingue, David A. Hinds, Magnus Johannesson, Amy K. Kiefer, David Laibson, Patrik K. E. Magnusson, Joanna L. Mountain, Sven Oskarsson, Olga Rostapshova, Alexander Teumer, Joyce Y. Tung, Peter M. Visscher, Daniel J. Benjamin, David Cesarini, Philipp D. Koellinger, N. Eriksson, D. A. Hinds, A. K. Kiefer, J. L. Mountain, J. Y. Tung, S. E. Medland, A. A. E. Vinkhuyzen, J. Yang, P. M. Visscher, D. Conley, J. D. Boardman, C. T. Dawes, B. W. Domingue, C. A. Rietveld, D. J. Benjamin, D. Cesarini, P. D. Koellinger, D. Conley, N. Eriksson, T. Esko, C. F. Chabris, M. Johannesson, D. Laibson, P. K. E. Magnusson, S. Oskarsson, O. Rostapshova, A. Teumer, P. M. Visscher, D. J. Benjamin, D. Cesarini, P. D. Koellinger
Institutions: Erasmus MC, Erasmus University Rotterdam, New York University, 23andMe (United States), University of Tartu, QIMR Berghofer Medical Research Institute, The University of Queensland, University of Colorado Boulder, University of Colorado Denver, Union College, Stockholm School of Economics, Harvard University, Karolinska Institutet, Uppsala University, Universitätsmedizin Greifswald, Universität Greifswald, Princess Alexandra Hospital, Cornell University, University of Amsterdam, Institute of Behavioral Sciences
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, Forskningsrådet för Arbetsliv och Socialvetenskap, U.S. Public Health Service, Economic and Social Research Council, National Institute on Aging, Office of Behavioral and Social Sciences Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Centre for Economic Performance 2010-2015, Infrastructure for Population Research, G4755840005, NBER Training Program in Aging and Health Economics, Understanding and Improving Healthcare Decision-Making and Outcomes for People Living with Alzheimer's Disease and Related Dementias, NBER Center for Aging and Health Research
OpenAlex ID: W2130272460