It is important to start by noting that people mean different things when they say gene–environment interaction. Before studying GxE interaction became so widespread, the phrase gene–environment interaction was sometimes used loosely to mean that genes and environments acted together to contribute to the outcome. This is entirely consistent with genes and environments having main effects, but there being no statistical interaction. The idea of there being a statistical interaction between genetic and environmental effects is the more recent and widespread meaning of gene–environment interaction. This indicates a situation where genetic and environmental effects are not independent of one another, but rather, the importance of one’s genetic predisposition varies as a function of environmental conditions, or alternately, the importance of the environment varies as a function of one’s genotype. It is important to note that these two alternate characterizations of GxE interaction are statistically indistinguishable. The key concept is one of dependence: one cannot understand the effect of genes without taking into account the environment, and one cannot understand the effect of the environment without taking into account genetic predispositions.
