Genotype-Based Bayesian Analysis of Gene-Environment Interactions with Multiple Genetic Markers and Misclassification in Environmental Factors.

Abstract

A key component to understanding etiology of complex diseases, such as cancer, diabetes, alcohol dependence, is to investigate gene-environment interactions. This work is motivated by the following two concerns in the analysis of gene-environment interactions. First, multiple genetic markers in moderate linkage disequilibrium may be involved in susceptibility to a complex disease. Second, environmental factors may be subject to misclassification. We develop a genotype based Bayesian pseudolikelihood approach that accommodates linkage disequilibrium in genetic markers and misclassification in environmental factors. Since our approach is genotype based, it allows the observed genetic information to enter the model directly thus eliminating the need to infer haplotype phase and simplifying computations. Bayesian approach allows shrinking parameter estimates towards prior distribution to improve estimation and inference when environmental factors are subject to misclassification. Simulation experiments demonstrated that our method produced parameter estimates that are nearly unbiased even for small sample sizes. An application of our method is illustrated using a case-control study of interaction between early onset of drinking and genes involved in dopamine pathway.