Effect of including environmental data in investigations of gene-disease associations in the presence of qualitative interactions.

Complex diseases are likely to be caused by the interplay of genetic and environmental factors. Despite this, gene-disease associations are frequently investigated using models that focus solely on a marginal gene effect, ignoring environmental factors entirely. Failing to take into account a gene-environment interaction can weaken the apparent gene-disease association, leading to loss in statistical power and, potentially, inability to identify genuine risk factors. If a gene-environment interaction exists, therefore, a joint analysis allowing the effect of the gene to differ between groups defined by the environmental exposure can have greater statistical power than a marginal gene-disease model. However, environmental data are subject to measurement error. Substantial losses in statistical power for detecting gene-environment interactions can arise from measurement error in the environmental exposure. It is unclear, however, what effect measurement error may have on the power of the joint analysis. We consider the potential benefits, in terms of statistical power, of collecting concurrent environmental data within large cohorts in order to enhance gene detection. We further consider whether these benefits remain in the presence of misclassification in both the gene and the environmental exposure. We find that when an effect of the gene is apparent only in the presence of the environmental exposure, the joint analysis has greater power than a marginal gene-disease analysis. This comparative increase in power remains in the presence of likely levels of misclassification of either the gene or environmental exposure. (c) 2010 Wiley-Liss, Inc.