Costs and benefits of environmental data in investigations of gene-disease associations

The inclusion of environmental exposure data may be beneficial, in terms of statistical power, to investigation of gene-disease association when it exists. However, resources invested in obtaining exposure data could instead be applied to measure disease status and genotype on more subjects. In a cohort study setting, we consider the tradeoff between measuring only disease status and genotype for a larger study sample and measuring disease status, genotype, and environmental exposure for a smaller study sample, under the ‘Mendelian randomization’ assumption that the environmental exposure is independent of genotype in the study population. We focus on the power of tests for gene-disease association, applied in situations where a gene modifies risk of disease due to particular exposure without a main effect of gene on disease. Our results are equally applicable to exploratory genome-wide association studies and more hypothesis-driven candidate gene investigations. We further consider the impact of misclassification for environmental exposures. We find that under a wide range of circumstances research resources should be allocated to genotyping larger groups of individuals, to achieve a higher power for detecting presence of gene-environment interactions by studying genedisease association.Science, Faculty ofStatistics, Department ofGraduat