Meta-analysis of SNP-environment interaction with heterogeneity for overlapping data

Meta-analysis is a popular method used in genome-wide association studies, by which the results of multiple studies are combined to identify associations. This process generates heterogeneity. Recently, we proposed a random effect model meta-regression method (MR) to study the effect of single nucleotide polymorphism (SNP)-environment interactions. This method takes heterogeneity into account and produces high power. We also proposed a fixed effect model overlapping MR in which the overlapping data is taken into account. In the present study, a random effect model overlapping MR that simultaneously considers heterogeneity and overlapping data is proposed. This method is based on the random effect model MR and the fixed effect model overlapping MR. A new way of solving the logarithm of the determinant of covariance matrices in likelihood functions is also provided. Tests for the likelihood ratio statistic of the SNP-environment interaction effect and the SNP and SNP-environment joint effects are given. In our simulations, null distributions and type I error rates were proposed to verify the suitability of our method, and powers were applied to evaluate the superiority of our method. Our findings indicate that this method is effective in cases of overlapping data with a high heterogeneity.