An epidemiologic approach to gene-environment interaction

Abstract

This paper illustrates how epidemiologic principles can be used to investigate relationships between genetic susceptibility and other risk factors for disease. Five plausible models are described for relationships between genetic and environmental effects, and an example of a simple mendelian disorder that fits each model is given. Each model leads to a different set of predictions about disease risk in individuals with the genetic susceptibility alone, the risk factor alone, both, or neither. The risk predictions for the different models are described, and research designs for testing them are discussed.

Fig. 1

Five hypothetical relationships between genetic susceptibility to disease and risk factors for disease identified in epidemiologic studies. The genetic susceptibility may be either polygenic or due to a dominant, recessive, or X-linked major locus. The risk factor may be only one of many factors associated with disease risk, and may itself have either genetic or nongenetic origins.