Detecting the association between a set of variants and a phenotype of interest is the first and important step in genetic and genomic studies. Although it attracted a large amount of attention in the scientific community and several related statistical approaches have been proposed in the literature, powerful and robust statistical tests are still highly desired and yet to be developed in this area. In this paper, we propose a powerful and robust association test, which combines information from each individual single-nucleotide polymorphisms based on sequential independent burden tests. We compare the proposed approach with some popular tests through a comprehensive simulation study and real data application. Our results show that, in general, the new test is more powerful; the gain in detecting power can be substantial in many situations, compared to other methods.
Keywords: SKAT; genetic association; rare variant.
© 2019 John Wiley & Sons, Ltd.