On the substructure controls in rare variant analysis: Principal components or variance components?

ABSTRACT: Recent studies showed that population substructure (PS) can have more complex impact on rare variant tests and that similarity-based collapsing tests (e.g., SKAT) may suffer more severely by PS than burden-based tests. In this work, we evaluate the performance of SKAT coupling with principal components (PC) or variance components (VC) based PS correction methods. We consider confounding effects caused by PS including stratified populations, admixed populations, and spatially distributed nongenetic risk; we investigate which types of variants (e.g., common, less frequent, rare, or all variants) should be used to effectively control for confounding effects. We found that (i) PC-based methods can account for confounding effects in most scenarios except for admixture, although the number of su

SUBMITTER: Luo Y 

PROVIDER: S-EPMC5851819 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature