Burden Testing of Rare Variants Identified through Exome Sequencing via Publicly Available Control Data.

ABSTRACT: The genetic causes of many Mendelian disorders remain undefined. Factors such as lack of large multiplex families, locus heterogeneity, and incomplete penetrance hamper these efforts for many disorders. Previous work suggests that gene-based burden testing-where the aggregate burden of rare, protein-altering variants in each gene is compared between case and control subjects-might overcome some of these limitations. The increasing availability of large-scale public sequencing databases such as Genome Aggregation Database (gnomAD) can enable burden testing using these databases as controls, obviating the need for additional control sequencing for each study. However, there exist various challenges with using public databases as controls, including lack of individual-level data, differences

SUBMITTER: Guo MH 

PROVIDER: S-EPMC6174288 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature