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Genome-Wide Meta-Analysis of Joint Tests for Genetic and Gene-Environment Interaction EffectsAschard H.a · Hancock D.B.b · London S.J.b · Kraft P.a
aProgram in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Mass., bEpidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, N.C., USA Corresponding Author
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Background: There is growing interest in the study of gene-environment interactions in the context of genome-wide association studies (GWASs). These studies will likely require meta-analytic approaches to have sufficient power. Methods: We describe an approach for meta-analysis of a joint test for genetic main effects and gene-environment interaction effects. Using simulation studies based on a meta-analysis of five studies (total n = 10,161), we compare the power of this test to the meta-analysis of marginal test of genetic association and the meta-analysis of standard 1 d.f. interaction tests across a broad range of genetic main effects and gene-environment interaction effects. Results: We show that the joint meta-analysis is valid and can be more powerful than classical meta-analytic approaches, with a potential gain of power over 50% compared to the marginal test. The standard interaction test had less than 1% power in almost all the situations we considered. We also show that regardless of the test used, sample sizes far exceeding those of a typical individual GWAS will be needed to reliably detect genes with subtle gene-environment interaction patterns. Conclusion: The joint meta-analysis is an attractive approach to discover markers which may have been missed by initial GWASs focusing on marginal marker-trait associations.
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