UK Biobank Whole-Exome Sequence Binary Phenome Analysis with Robust Region-Based Rare-Variant Test.

ABSTRACT: In biobank data analysis, most binary phenotypes have unbalanced case-control ratios, and this can cause inflation of type I error rates. Recently, a saddle point approximation (SPA) based single-variant test has been developed to provide an accurate and scalable method to test for associations of such phenotypes. For gene- or region-based multiple-variant tests, a few methods exist that can adjust for unbalanced case-control ratios; however, these methods are either less accurate when case-control ratios are extremely unbalanced or not scalable for large data analyses. To address these problems, we propose SKAT- and SKAT-O- type region-based tests; in these tests, the single-variant score statistic is calibrated based on SPA and efficient resampling (ER). Through simulation studies, we sh

SUBMITTER: Zhao Z 

PROVIDER: S-EPMC7042481 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature