Federated analysis of autosomal recessive coding variants in 29,745 developmental disorder patients from diverse populations.

ABSTRACT: Autosomal recessive coding variants are well-known causes of rare disorders. We quantified the contribution of these variants to developmental disorders in a large, ancestrally diverse cohort comprising 29,745 trios, of whom 20.4% had genetically inferred non-European ancestries. The estimated fraction of patients attributable to exome-wide autosomal recessive coding variants ranged from ~2-19% across genetically inferred ancestry groups and was significantly correlated with average autozygosity. Established autosomal recessive developmental disorder-associated (ARDD) genes explained 84.0% of the total autosomal recessive coding burden, and 34.4% of the burden in these established genes was explained by variants not already reported as pathogenic in ClinVar. Statistical analyses identified

SUBMITTER: Chundru VK 

PROVIDER: S-EPMC11525179 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature