A Powerful Variant-Set Association Test Based on Chi-Square Distribution

Detecting the association between a set of variants and a given phenotype has attracted a large amount of attention in the scientific community, although it is a difficult task. Recently, several related statistical approaches have been proposed in the literature; powerful statistical tests are still highly desired and yet to be developed in this area. In this paper, we propose a powerful test that combines information from each individual single nucleotide polymorphism (SNP) based on principal component analysis without relying on the eigenvalues associated with the principal components. We compare the proposed approach with some popular tests through a simulation study and real data applications. Our results show that, in general, the new test is more powerful than its competitors considered in this study; the gain in detecting power can be substantial in many situations.