Estimating clinical risk in gene regions from population sequencing cohort data.

ABSTRACT: While pathogenic variants can significantly increase disease risk, it is still challenging to estimate the clinical impact of rare missense variants more generally. Even in genes such as BRCA2 or PALB2, large cohort studies find no significant association between breast cancer and rare missense variants collectively. Here, we introduce REGatta, a method to estimate clinical risk from variants in smaller segments of individual genes. We first define these regions by using the density of pathogenic diagnostic reports and then calculate the relative risk in each region by using over 200,000 exome sequences in the UK Biobank. We apply this method in 13 genes with established roles across several monogenic disorders. In genes with no significant difference at the gene level, this approach signi

SUBMITTER: Fife JD 

PROVIDER: S-EPMC10257006 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature