Cross-Disorder Analysis of De Novo Variants Increases the Power of Prioritising Candidate Genes.

ABSTRACT: De novo variants (DNVs) are critical to the treatment of neurodevelopmental disorders (NDDs). However, effectively identifying candidate genes in small cohorts is challenging in most NDDs because of high genetic heterogeneity. We hypothesised that integrating DNVs from multiple NDDs with genetic similarity can significantly increase the possibility of prioritising the candidate gene. We catalogued 66,186 coding DNVs in 50,028 individuals with nine types of NDDs in cohorts with sizes spanning from 118 to 31,260 from Gene4Denovo database to validate this hypothesis. Interestingly, we found that integrated DNVs can effectively increase the number of prioritised candidate genes for each disorder. We identified 654 candidate genes including 481 shared candidate genes carrying putative functiona

SUBMITTER: Li K 

PROVIDER: S-EPMC8001830 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature