Most human complex phenotypes result from multiple genetic and environmental factors and their interactions. Understanding the mechanisms by which genetic and environmental factors interact offers valuable insights into the genetic architecture of complex traits and holds great potential for advancing precision medicine. The emergence of large population biobanks has led to the development of numerous statistical methods aiming at identifying gene-environment interactions (G × E). In this review, we present state-of-the-art statistical methodologies for G × E analysis. We will survey a spectrum of approaches for single-variant G × E mapping, followed by various techniques for polygenic G × E analysis. We conclude this review with a discussion on the future directions and challenges in G × E research.
Keywords: Applications of Computational Statistics > Genomics/Proteomics/Genetics; Data: Types and Structure > Massive Data; Statistical Models > Linear Models; gene–environment interaction (G × E); precision medicine; statistical genetics.