These explanations for the variation in disease liability are not mutually exclusive; part of the variance may be explained by the additive actions of genes and environment and another part by their interaction. The properties of such complex models are a mixture of the characteristics of the three basic models, and we limit ourselves to the presentation of these basic models. In discussing some of the predictions based on these models, it is assumed that the environment can be dichotomized into ‘protective’ or ‘predisposing’, and that environmental risk can be assessed in the proband (the index case or patient from whom other family members are identified) and in his or her relatives.