A general framework for identifying oligogenic combinations of rare variants in complex disorders.

ABSTRACT: Genetic studies of complex disorders such as autism and intellectual disability (ID) are often based on enrichment of individual rare variants or their aggregate burden in affected individuals compared to controls. However, these studies overlook the influence of combinations of rare variants that may not be deleterious on their own due to statistical challenges resulting from rarity and combinatorial explosion when enumerating variant combinations, limiting our ability to study oligogenic basis for these disorders. Here, we present RareComb, a framework that combines the Apriori algorithm and statistical inference to identify specific combinations of mutated genes associated with complex phenotypes. RareComb overcomes computational barriers and exhaustively evaluates variant combinations

SUBMITTER: Pounraja VK 

PROVIDER: S-EPMC9104696 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature