An allelic-series rare-variant association test for candidate-gene discovery.

ABSTRACT: Allelic series are of candidate therapeutic interest because of the existence of a dose-response relationship between the functionality of a gene and the degree or severity of a phenotype. We define an allelic series as a collection of variants in which increasingly deleterious mutations lead to increasingly large phenotypic effects, and we have developed a gene-based rare-variant association test specifically targeted to identifying genes containing allelic series. Building on the well-known burden test and sequence kernel association test (SKAT), we specify a variety of association models covering different genetic architectures and integrate these into a Coding-Variant Allelic-Series Test (COAST). Through extensive simulations, we confirm that COAST maintains the type I error and improv

SUBMITTER: McCaw ZR 

PROVIDER: S-EPMC10432147 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature