# Deciphering genetic susceptibility to clear cell renal cell carcinoma

## TL;DR

This study identifies genes and biological pathways linked to kidney cancer risk by combining genetic and chromatin data.

## Contribution

The study uses the ABC model with renal-specific data to reveal enhancer-gene relationships in clear cell renal cell carcinoma.

## Key findings

- Variation in hypoxia sensing pathways mediates clear cell renal cell carcinoma risk.
- Cell cycle regulation and telomerase maintenance are central to ccRCC susceptibility.
- Integration of GWAS and chromatin data identifies target genes for ccRCC.

## Abstract

Genome-wide association studies (GWAS) have identified over 60 autosomal risk loci associated with clear cell renal cell carcinoma (ccRCC), yet the functional mechanisms underlying these associations remain largely unclear. To establish connections between risk variants and their target genes, we applied the activity-by-contact (ABC) model, which integrates epigenomic data and Micro-C interactions, complemented with renal-specific quantitative trait loci, to predict enhancer-gene relationships. Our analyses implicate variation in hypoxia sensing, cell cycle regulation, and telomerase maintenance pathways as central mediators of ccRCC risk. These findings provide new insights into the molecular basis of ccRCC susceptibility and highlight potential therapeutic avenues for prevention and treatment.

Integration of genome-wide association data with epigenomic and chromatin interaction data identifies target genes mediating clear cell renal cell carcinoma risk, implicating disrupted hypoxia signalling, cell cycle, and telomerase regulation.