Prioritizing context-specific genetic risk mechanisms in 11 solid cancers.

ABSTRACT:

Background

While genome-wide association studies (GWAS) have identified hundreds of cancer-associated genetic variants, the specific biological contexts where these variants exert their effects remain largely unknown. We aimed to prioritize context-specific genetic risk mechanisms for 11 solid cancers at both genome-wide and single-variant resolutions.

Methods

We integrated cancer GWAS summary statistics from European ancestry samples (avg. n cases=47,856) with ~1,500 context-specific annotations representing candidate cis-regulatory elements. For genome-wide analysis, we applied CT-FM, a method that leverages heritability enrichment estimates and an annotation correlation matrix to select likely disease-relevant biological contexts. After identifying putative causal

SUBMITTER: Wu X 

PROVIDER: S-EPMC12636666 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature