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• W4387019576 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." @default.
• W4387019576 created "2023-09-26" @default.
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• W4387019576 date "2023-09-25" @default.
• W4387019576 modified "2023-10-05" @default.
• W4387019576 title "Genome-wide enhancer-gene regulatory maps link causal variants to target genes underlying human cancer risk" @default.
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• W4387019576 doi "https://doi.org/10.1038/s41467-023-41690-z" @default.
• W4387019576 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37749132" @default.
• W4387019576 hasPublicationYear "2023" @default.
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