Gene-Environment Interaction: A Variable Selection Perspective

Methods Mol Biol. 2021:2212:191-223. doi: 10.1007/978-1-0716-0947-7_13.

Abstract

Gene-environment interactions have important implications for elucidating the genetic basis of complex diseases beyond the joint function of multiple genetic factors and their interactions (or epistasis). In the past, G × E interactions have been mainly conducted within the framework of genetic association studies. The high dimensionality of G × E interactions, due to the complicated form of environmental effects and the presence of a large number of genetic factors including gene expressions and SNPs, has motivated the recent development of penalized variable selection methods for dissecting G × E interactions, which has been ignored in the majority of published reviews on genetic interaction studies. In this article, we first survey existing studies on both gene-environment and gene-gene interactions. Then, after a brief introduction to the variable selection methods, we review penalization and relevant variable selection methods in marginal and joint paradigms, respectively, under a variety of conceptual models. Discussions on strengths and limitations, as well as computational aspects of the variable selection methods tailored for G × E studies, have also been provided.

Keywords: Bayesian variable selection; Gene–environment interaction; Linear and nonlinear interaction; Marginal and joint analysis; Penalization.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Algorithms
  • Bayes Theorem
  • Computer Simulation
  • Epistasis, Genetic*
  • Gene-Environment Interaction*
  • Genome-Wide Association Study
  • Humans
  • Linear Models*
  • Models, Genetic*
  • Nonlinear Dynamics*
  • Polymorphism, Single Nucleotide