The contribution of coding variants to the heritability of multiple cancer types using UK Biobank whole-exome sequencing data.

ABSTRACT: Genome-wide association studies have been highly successful at identifying common variants associated with cancer; however, they do not explain all the inherited risks of cancer. Family-based studies, targeted sequencing, and, more recently, exome-wide association studies have identified rare coding variants in some genes associated with cancer risk, but the overall contribution of these variants to the heritability of cancer is less clear. Here, we describe a method to estimate the genome-wide contribution of rare coding variants to heritability that fits models to the burden effect sizes using an empirical Bayesian approach. We apply this method to the burden of protein-truncating variants in over 15,000 genes for 11 cancers in the UK Biobank using whole-exome sequencing data on over 400

SUBMITTER: Wilcox N 

PROVIDER: S-EPMC12081281 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature