Small sample sizes are a common problem in molecular epidemiologic studies.[41] However, the limitations imposed by small samples size are particularly acute when considering epigenetic studies because of the inherent potential for confounding by both environmental factors as well as genotypes in these studies. In this way, the requirement of adjusting for these multiple potential confounders increases the number of degrees of freedom used in regression models, imposing a lower bound on tenable sample sizes in epigenetic studies. Moreover, as above in our discussion of causal models, testing epigenetic hypotheses implies mediation analysis, requiring larger sample sizes than simple exposure-outcome assessments in epidemiologic studies.
