Identification of rare causal variants in sequence-based studies: methods and applications to VPS13B, a gene involved in Cohen syndrome and autism.

ABSTRACT: Pinpointing the small number of causal variants among the abundant naturally occurring genetic variation is a difficult challenge, but a crucial one for understanding precise molecular mechanisms of disease and follow-up functional studies. We propose and investigate two complementary statistical approaches for identification of rare causal variants in sequencing studies: a backward elimination procedure based on groupwise association tests, and a hierarchical approach that can integrate sequencing data with diverse functional and evolutionary conservation annotations for individual variants. Using simulations, we show that incorporation of multiple bioinformatic predictors of deleteriousness, such as PolyPhen-2, SIFT and GERP++ scores, can improve the power to discover truly causal varian

SUBMITTER: Ionita-Laza I 

PROVIDER: S-EPMC4263785 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature