Allele-specific epigenetic activity in prostate cancer and normal prostate tissue implicates prostate cancer risk mechanisms

• DOI: 10.1101/2021.06.02.446619
• Publication Date: 2021-06-12T00:15:21Z
• Authors: Anamay Shetty; Ji-Heui Seo; Connor A. Bell; Edward P. O’Connor; Mark Pomerantz; Matthew L. Freedman; Alexander Gusev
• Keywords: Genome-wide Association Study; Epigenomics

Abstract Background Genome-wide association studies of prostate cancer have identified >250 significant risk loci, but the causal variants and mechanisms for these loci remain largely unknown. Here, we sought to identify characterize harboring regulatory elements by integrating epigenomes from primary tumor normal tissues 27 patients across H3K27ac, H3K4me3, H3K4me2 histone marks FOXA1 HOXB13 transcription factors. Results We 7,371 peaks with allele-specificity (asQTL peaks). Showcasing their relevance risk, H3K27ac T-asQTL were single annotation most enriched GWAS heritability (40x), significantly higher than corresponding non-asQTL (14x) or coding regions (14x). Surprisingly, fine-mapped asQTL observed in tumors, including that differentially imbalanced respect tumor-normal states. These data pinpointed putative at 20 which 11 detected only samples. More broadly, tumor-specific asQTLs expression QTLs benign as well accessible found stem cells, supporting a hypothesis where some germline become reactivated during/after transformation can be captured epigenomic profiling tumor. Conclusion Our study demonstrates power chromatin signals uncover mechanisms, highlights regulation context prioritizes multiple experimental follow-up.