High-Dimensional Gene-Environment Interaction Analysis

Beyond the main genetic and environmental effects, gene-environment (G-E) interactions have been demonstrated to significantly contribute to the development and progression of complex diseases. Published analyses of G-E interactions have primarily used a supervised framework to model both low-dimensional environmental factors and high-dimensional genetic factors in relation to disease outcomes. In this article, we aim to provide a selective review of methodological developments in G-E interaction analysis from a statistical perspective. The three main families of techniques are hypothesis testing, variable selection, and dimension reduction, which lead to three general frameworks: testing-based, estimation-based, and prediction-based. Linear- and nonlinear-effects analysis, fixed- and random-effects analysis, marginal and joint analysis, and Bayesian and frequentist analysis are reviewed to facilitate the conduct of interaction analysis in a wide range of situations with various assumptions and objectives. Statistical properties, computations, applications, and future directions are also discussed.