Enhancer RNA Transcriptome-Wide Association Study Reveals a Distinctive Class of Pan-Cancer Susceptibility eRNAs.

ABSTRACT: Many cancer risk variants are located within enhancer regions and lack sufficient molecular interpretation. Here, we constructed the first comprehensive atlas of enhancer RNA (eRNA)-mediated genetic effects from 28 033 RNA sequencing samples across 11 606 individuals, identifying 21 073 eRNA quantitative trait loci (eRNA-QTLs) significantly associated with eRNA expression. Mechanistically, eRNA-QTLs frequently altered binding motifs of transcription factors. In addition, 28.48% of cancer risk variants are strongly colocalized with eRNA-QTLs. A pan-cancer eRNA-based transcriptome-wide association study is conducted across 23 major cancer types, identifying 626 significant cancer susceptibility eRNAs predicted to modulate cancer risk via eRNA, from which 54.90% of the eRNA target genes are o

SUBMITTER: Chen W 

PROVIDER: S-EPMC11967800 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature