X-linked repeat polymorphisms and disease risk: Statistical power and study designs

Unrestricted The design and analysis of association studies for repeat polymorphisms has received scant attention in the literature. We present an analytical power calculation for studies of such polymorphisms, based on a case-parent design and an X-linked polymorphism. Existing tools for estimating statistical power in family-based studies (such as Quanto) presume categorical codings of autosomal loci. We extend the underlying method to handle quantitative codings of repeat polymorphisms, and discuss the advantages of doing so. Sample sizes for a conditional logistic regression analysis of a sex-linked repeat polymorphism in a case-parent design are presented. Empirical power for quantitative and categorical codings of the same polymorphism with the same sample size in otherwise identical studies are then compared via Monte Carlo simulation. The differences in information to be expected from male and female case-parent, case-sibling, and case-population pairs are discussed. In addition, the effects of stratification and model mis-specification are explored. The effects of missing data, and potential approaches for addressing it, are discussed.