Establishing the role of gene-environment interactions in the etiology of type 2 diabetes

The descriptive epidemiology of Type 2 diabetes strongly suggests that this condition arises as a result of a complex interaction between genetic and environmental factors, Although family based studies are appropriate as a means of detecting genetic effects, they are not suitable for identifying interactions between genes and factors such as diet and physical inactivity. Cross-sectional case-control studies are not appropriate as they will be affected by recall bias of lifestyle pattern,; among people who have been labelled as having diabetes. Nested case-control studies, although not affected by recall bias, will be lengthy and expensive, The alternative approach of using the quantitative trait, that Underlie diabetes, such as insulin resistance, to detect gene-environment interaction is likely to be a quicker and more powerful strategy provided the search for interaction is based on biologic understanding and is combined with case-control approaches that allow the magnitude of effects on disease risk to be quantified in parallel. The recent reports concerning the common polymorphism in the PPARgamma gene illustrate the strength of this strategy. The power to detect gene-environment interactions on quantitative traits is a major consideration, and perhaps the most important determinants are the precision with which the continuously distributed exposure and outcome measures are assessed. Investment in studies with better measurement may be a superior strategy than simply designing ever larger studies.