Meta-Analysis of SNP-Environment Interaction With Overlapping Data.

Meta-analysis, which combines the results of multiple studies, is an important analytical method in genome-wide association studies. In genome-wide association studies practice, studies employing meta-analysis may have overlapping data, which could yield false positive results. Recent studies have proposed models to handle the issue of overlapping data when testing the genetic main effect of single nucleotide polymorphism. However, there is still no meta-analysis method for testing gene-environment interaction when overlapping data exist. Inspired by the methods of testing the main effect of gene with overlapping data, we proposed an overlapping meta-regulation method to address the issue in testing the gene-environment interaction. We generalized the covariance matrices of the regular meta-regression model by employing Lin's and Han's correlation structures to incorporate the correlations introduced by the overlapping data. Based on our proposed models, we further provided statistical significance tests of the gene-environment interaction as well as joint effects of the gene main effect and the interaction. Through simulations, we examined type I errors and statistical powers of our proposed methods at different levels of data overlap among studies. We demonstrated that our method well controls the type I error and simultaneously achieves statistical power comparable with the method that removes overlapping samples