The goal of this work is to explore the power of a range of study designs to discover novel genetic and environmental resistance factors. Those study designs include case-control, representative sampling, a low risk-design, and the high-risk design. We also examine modifications of the high-risk design, an approach where subjects are selected based on the presence of a phenotype of interest in a parent. The intent of the high-risk design is to enrich for “risk” factors, both genetic and family-environment, to increase the probability of disease outcomes in the offspring. We treat the case-control design as the reference approach, since it is the most widely used approach to over-ascertainment of cases relative to population prevalence in order to gain power. For resistance studies, we explore whether sampling based on environmental exposures and parental phenotype impacts the power to detect specific genetic and environmental resistance factors. We use a simulation-based approach and assume an underlying continuous disease liability to compare the power to detect novel resistance factors under each study design.
