Exome-wide evaluation of rare coding variants using electronic health records identifies new gene-phenotype associations.

ABSTRACT: The clinical impact of rare loss-of-function variants has yet to be determined for most genes. Integration of DNA sequencing data with electronic health records (EHRs) could enhance our understanding of the contribution of rare genetic variation to human disease¹. By leveraging 10,900 whole-exome sequences linked to EHR data in the Penn Medicine Biobank, we addressed the association of the cumulative effects of rare predicted loss-of-function variants for each individual gene on human disease on an exome-wide scale, as assessed using a set of diverse EHR phenotypes. After discovering 97 genes with exome-by-phenome-wide significant phenotype associations (P < 10^-6), we replicated 26 of these in the Penn Medicine Biobank, as well as in three other medical biobanks and t

SUBMITTER: Park J 

PROVIDER: S-EPMC8775355 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature