Optimal unified approach for rare-variant association testing with application to small-sample case-control whole-exome sequencing studies.

ABSTRACT: We propose in this paper a unified approach for testing the association between rare variants and phenotypes in sequencing association studies. This approach maximizes power by adaptively using the data to optimally combine the burden test and the nonburden sequence kernel association test (SKAT). Burden tests are more powerful when most variants in a region are causal and the effects are in the same direction, whereas SKAT is more powerful when a large fraction of the variants in a region are noncausal or the effects of causal variants are in different directions. The proposed unified test maintains the power in both scenarios. We show that the unified test corresponds to the optimal test in an extended family of SKAT tests, which we refer to as SKAT-O. The second goal of this paper is to

SUBMITTER: Lee S 

PROVIDER: S-EPMC3415556 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature