Unknown

Dataset Information

0

Genome-wide enhancer-gene regulatory maps link causal variants to target genes underlying human cancer risk.


ABSTRACT: Genome-wide association studies have identified numerous variants associated with human complex traits, most of which reside in the non-coding regions, but biological mechanisms remain unclear. However, assigning function to the non-coding elements is still challenging. Here we apply Activity-by-Contact (ABC) model to evaluate enhancer-gene regulation effect by integrating multi-omics data and identified 544,849 connections across 20 cancer types. ABC model outperforms previous approaches in linking regulatory variants to target genes. Furthermore, we identify over 30,000 enhancer-gene connections in colorectal cancer (CRC) tissues. By integrating large-scale population cohorts (23,813 cases and 29,973 controls) and multipronged functional assays, we demonstrate an ABC regulatory variant rs4810856 associated with CRC risk (Odds Ratio = 1.11, 95%CI = 1.05-1.16, P = 4.02 × 10-5) by acting as an allele-specific enhancer to distally facilitate PREX1, CSE1L and STAU1 expression, which synergistically activate p-AKT signaling. Our study provides comprehensive regulation maps and illuminates a single variant regulating multiple genes, providing insights into cancer etiology.

SUBMITTER: Ying P 

PROVIDER: S-EPMC10520073 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications


Genome-wide association studies have identified numerous variants associated with human complex traits, most of which reside in the non-coding regions, but biological mechanisms remain unclear. However, assigning function to the non-coding elements is still challenging. Here we apply Activity-by-Contact (ABC) model to evaluate enhancer-gene regulation effect by integrating multi-omics data and identified 544,849 connections across 20 cancer types. ABC model outperforms previous approaches in lin  ...[more]

Similar Datasets

2023-01-17 | GSE222770 | GEO
2023-01-17 | GSE222769 | GEO
2023-01-17 | GSE222766 | GEO
2023-01-17 | GSE222768 | GEO
| S-EPMC9153265 | biostudies-literature
| PRJNA923334 | ENA
| PRJNA923343 | ENA
| PRJNA923340 | ENA
| PRJNA923341 | ENA
2021-03-01 | GSE155555 | GEO