Rare-variant extensions of the transmission disequilibrium test: application to autism exome sequence data.

ABSTRACT: Many population-based rare-variant (RV) association tests, which aggregate variants across a region, have been developed to analyze sequence data. A drawback of analyzing population-based data is that it is difficult to adequately control for population substructure and admixture, and spurious associations can occur. For RVs, this problem can be substantial, because the spectrum of rare variation can differ greatly between populations. A solution is to analyze parent-child trio data, by using the transmission disequilibrium test (TDT), which is robust to population substructure and admixture. We extended the TDT to test for RV associations using four commonly used methods. We demonstrate that for all RV-TDT methods, using proper analysis strategies, type I error is well-controlled even whe

SUBMITTER: He Z 

PROVIDER: S-EPMC3882934 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature