Gene-based and pathway-based testing for rare-variant association in affected sib pairs.

ABSTRACT: Next generation sequencing technologies have made it possible to investigate the role of rare variants (RVs) in disease etiology. Because RVs associated with disease susceptibility tend to be enriched in families with affected individuals, study designs based on affected sib pairs (ASP) can be more powerful than case-control studies. We construct tests of RV-set association in ASPs for single genomic regions as well as for multiple regions. Single-region tests can efficiently detect a gene region harboring susceptibility variants, while multiple-region extensions are meant to capture signals dispersed across a biological pathway, potentially as a result of locus heterogeneity. Within ascertained ASPs, the test statistics contrast the frequencies of duplicate rare alleles (usually appearing

SUBMITTER: Romanescu RG 

PROVIDER: S-EPMC7318298 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature