Evaluation of the power and type I error of recently proposed family-based tests of association for rare variants

Until very recently, few methods existed to analyze rare-variant association with binary phenotypes in complex pedigrees. We consider a set of recently proposed methods applied to the simulated and real hypertension phenotype as part of the Genetic Analysis Workshop 18. Minimal power of the methods is observed for genes containing variants with weak effects on the phenotype. Application of the methods to the real hypertension phenotype yielded no genes meeting a strict Bonferroni cutoff of significance. Some prior literature connects 3 of the 5 most associated genes (p <1 × 10(−4)) to hypertension or related phenotypes. Further methodological development is needed to extend these methods to handle covariates, and to explore more powerful test alternatives.