Gene x environment interaction from case-control and case-case approaches

Using the Genetic Analysis Workshop 12 data, we applied case-control and ca se-case approaches to study the effects of a major gene and its interaction with sex on the disease liability. Although no joint additive effect was s imulated, the case-case approach detected a small but significant multiplic ative interaction effect, which could not be explained by the effect of ran dom error. Given that analyses of "real" data will not be made with the kno wledge of the true effects a priori, this study showed that the measure of gene x environment interaction is critical and the definition of interactio n should be explicit. (C) 2001 Wiley-Liss, Inc.