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Genome\u2010wide association studies (GWAS) identify multiple susceptibility loci, but most map to noncoding regions, leaving variant\u2010to\u2010gene links unresolved. In this study, a genome\u2010wide regulatory map is constructed using expression quantitative trait loci (eQTL) analysis of 482 pancreatic tissues, and integrated with a GWAS meta\u2010analysis to prioritize causal variants. A total of 82 significant variants and 15 target genes for pancreatic cancer risk are identified, with enrichment in cancer\u2010related pathways. The variant rs11102484 is validated in an independent cohort of 569 cases and 2691 controls. The combined analysis of 5699 cases and 8467 controls confirms that the G allele of rs11102484 significantly reduces pancreatic cancer risk (odds ratio = 0.85, 95% confidence interval = 0.80\u20130.90,\n                    <jats:italic>P<\/jats:italic>\n                    = 4.83 \u00d7 10\n                    <jats:sup>\u22128<\/jats:sup>\n                    ). Functional assays demonstrate that the G allele impairs ZNF263 binding at rs11102484, thereby weakening a long\u2010range silencer\u2010promoter interaction and increasing\n                    <jats:italic>ST7L<\/jats:italic>\n                    expression. Elevated\n                    <jats:italic>ST7L<\/jats:italic>\n                    dampens AKT\/\u03b2\u2010catenin signaling and suppresses pancreatic cancer cell proliferation, consistent with the protective association. Overall, this study implicates functional genes in pancreatic cancer risk and characterizes a regulatory variant that modulates\n                    <jats:italic>ST7L<\/jats:italic>\n                    expression, advancing the interpretation of GWAS findings and understanding of pancreatic cancer biology.\n                  <\/jats:p>","DOI":"10.1002\/advs.202517184","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T18:49:36Z","timestamp":1773427776000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mapping Genetic Regulation of Transcription to Identify Functional Variants and Genes Associated with Pancreatic Cancer Risk"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiaoyang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics School of Public Health Wuhan University  Wuhan China"},{"name":"Department of Cancer 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School of Public Health Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zequn","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics School of Public Health Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangshuang","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics School of Public Health Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics School of Public Health Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cancer Epidemiology The Affiliated Cancer Hospital of Zhengzhou University &amp; Henan Cancer Hospital  Zhengzhou China"},{"name":"College of Public Health Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxi","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Cancer Epidemiology The Affiliated Cancer Hospital of Zhengzhou University &amp; Henan Cancer Hospital  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics School of Public Health Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics School of Public Health Wuhan University  Wuhan China"},{"name":"State Key Laboratory of Metabolism and Regulation in Complex Organisms TaiKang Center for Life and Medical Sciences, Wuhan University  Wuhan 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