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.