Long-range chromatin interactions nominate candidate susceptibility genes at non-coding PDAC risk loci

Long-range chromatin interactions at non-coding PDAC risk loci nominate 273 candidate target genes, including a ~280 kb SOX9-linked interaction and a ~900 kb INHBA enhancer link.

• Why it matters: GWAS loci for pancreatic ductal adenocarcinoma leave functional variants and target genes unclear, limiting mechanistic interpretation of non-coding risk signals.
• What they did: The study fine-mapped 1,414 variants across 31 PDAC signals and used GWAS Capture-C to connect variants to 2,108 transcripts at 25 loci, plus CRISPR inhibition of four fine-mapped variants at 7p14.1.
• The result: At 7p14.1, rs12701838 is linked to INHBA expression (NES = 0.22, P = 1.5x10-5), and CRISPR inhibition reduced INHBA, supporting a distal enhancer mechanism and suggesting inflammatory signaling may underlie risk.

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