It is important to first address some aspects of terminology surrounding the study of gene-environment interaction. In lay terms, the phrase gene-environment interaction is often used to mean that both genes and environments are important. In statistical terms, this does not necessarily indicate an interaction but could be consistent with an additive model, in which there are main effects of the environment and main effects of genes. But in a statistical sense an interaction is a very specific thing, referring to a situation in which the effect of one variable cannot be understood without taking into account the other variable. Their effects are not independent. When we refer to gene-environment interaction in a statistical sense, we are referring to a situation in which the effect of genes depends on the environment and/or the effect of the environment depends on genotype. We note that these two alternative conceptualizations of gene-environment interaction are indistinguishable statistically. It is this statistical definition of gene-environment interaction that is the primary focus of this review (except where otherwise noted).
