Figure 2

Putative gene-environment interactions. For even the simplest case, a dichotomous genetic risk factor (for example, carriers versus non-carriers) and a dichotomous environmental risk factor (for example, present versus absent), several types of interactions are possible. If both the gene and environment have main effects (odds ratios > 1), and thus could be identified independently, a synergistic interaction would result in an effect size larger than a simple additive effect. A second possibility is that an environmental factor could have no main effect but could modify the effect of a genetic factor that does have a main effect, creating a larger than expected combined effect. The inverse is also possible, in which a modifier gene with no main effect of its own increases the effect size of an environmental risk factor. A fourth possibility is that neither the gene nor the environment has a detectable main effect, and interaction is required to produce a measurable effect. A fifth possibility is for a gene and an environmental factor to have redundant effects, in which case the combination of factors produces no increase in risk. These types of interactions can be extended to include different effect sizes or gene-gene interactions.