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

ABSTRACT: While pathogenic variants significantly increase disease risk in many genes, 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 germline missense variants collectively. Here we introduce REGatta, a method to improve the estimation of clinical risk in gene segments. We define gene regions using the density of pathogenic diagnostic reports, and then calculate the relative risk in each of these regions using 109,581 exome sequences from women in the UK Biobank. We apply this method in seven established breast cancer genes, and identify regions in each gene with statistically significant differences in breast can

SUBMITTER: Fife JD 

PROVIDER: S-EPMC9882564 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature