Printed in USA. Sample Size Requirements in Case-Only Designs to Detect Gene- Environment Interaction

With advances in molecular genetic technology, more studies will examine gene-environment interaction in disease etiology. If the primary purpose of the study is to estimate the effect of gene-environment interaction in disease etiology, one can do so without employing controls. The case-only design has been promoted as an efficient and valid method for screening for gene-environment interaction. The authors derive a method for estimating sample size requirements, present sample size estimates, and compare minimum sample size requirements to detect gene-environment interaction in case-only studies with case-control studies. Assuming independence between exposure and genotype in the population, the authors believe that the case-only design is more efficient than a case-control design in detecting gene-environment interaction. They also illustrate a method to estimate sample size when information on marginal effects (relative risk) of exposure and genotype is available from previous studies. Am J Epidemiol 1997;146:713-20. case-control studies; epidemiologic methods; gene-environment interaction; genes; sample size With advances in molecular genetic technology, ge-netic markers have been used increasingly in case-control studies to search for gene-environment inter-action (1-8). Concerns about selecting appropriat