{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T19:57:24Z","timestamp":1790452644910,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Food Science &amp;amp; Nutrition"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The contribution of circulating micronutrients to ulcer susceptibility remains poorly defined across anatomical sites. In this study, we constructed a systematic trace element\u2013ulcer map by integrating genetic\u2010instrumented inference, pleiotropy\u2010aware modeling, and heterogeneity\u2010sensitive clustering. Summary\u2010level data were obtained from large\u2010scale genome\u2010wide association studies (GWAS)\u00a0encompassing 10 circulating micronutrients (calcium, iron, zinc, copper, magnesium, selenium, carotene, vitamin B12, vitamin C, and vitamin D) and nine ulcer phenotypes (corneal ulcer, recurrent oral aphthae, esophageal ulcer, gastric ulcer, duodenal ulcer, vaginal\/vulvar ulcer, decubitus ulcer, lower limb ulcer, and chronic skin ulcer), covering more than 3 million individuals of European ancestry. Our two\u2010sample Mendelian randomization (MR) analysis identified genetically elevated zinc levels as a risk factor for gastric (OR: 1.141, 95% CI: 1.060\u20131.228,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20094.57\u2009\u00d7\u200910\n                    <jats:sup>\u22124<\/jats:sup>\n                    ) and esophageal ulcers, but inversely associated with vaginal\/vulvar ulcer risk. Protective effects were observed for iron with gastric ulcers and calcium with duodenal ulcers. Carotene and magnesium were nominally associated with increased risk of oral aphthae and vaginal ulcers, respectively. To refine these associations, we applied Causal Analysis Using Summary Effect estimates (CAUSE) and MR\u2010Clust. While CAUSE did not confirm robust putative causal relationships in most pairs, MR\u2010Clust uncovered three distinct SNP clusters in the vitamin C\u2010corneal ulcer pair, indicating potential mechanistic heterogeneity. These pleiotropy\u2010aware and cluster\u2010based approaches enhanced the interpretability of borderline signals and revealed genetic heterogeneity beyond mean\u2010effect estimates. Collectively, this study offers a panoramic view of trace element\u2010ulcer relationships and prioritizes zinc as a key candidate for further mechanistic exploration in gastric ulcer pathogenesis. Our integrative framework may serve as a foundation for future etiological and nutritional intervention studies.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.71094","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T12:00:33Z","timestamp":1761912033000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Trace Element\u2013Ulcer Map: Decoding Micronutrient\u2013Ulcer Relationships Through Genetic Architecture and Pleiotropy\u2010Aware Inference"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4498-8978","authenticated-orcid":false,"given":"Xueyao","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Plastic Surgery The Third Xiangya Hospital of Central South University  Changsha Hunan 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Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianda","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery The Third Xiangya Hospital of Central South University  Changsha Hunan 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