The oligogenic inheritance test GCOD detects risk genes and their interactions in congenital heart defects.

ABSTRACT: Exome sequencing of thousands of families has revealed many risk genes for congenital heart defects (CHDs), yet most cases cannot be explained by a single causal mutation. Even within the same family, individuals carrying a particular mutation in a known risk gene often demonstrate variable phenotypes, suggesting the presence of genetic modifiers. To explore oligogenic causes of CHD without assessing billions of variant combinations, we develop an efficient, simulation-based method to detect gene sets that carry co-occurring damaging variants in probands at a higher rate than expected given parental genotypes. We implement this approach in software called Gene Combinations in Oligogenic Disease (GCOD) and apply it to a cohort of 3377 CHD trios with exome sequencing. This analysis detects 1

SUBMITTER: Pittman M 

PROVIDER: S-EPMC12863180 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature