{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:08:40Z","timestamp":1789150120461,"version":"build-2803163510"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jiangxi Provincial Traditional Chinese Medicine Administration Science and Technology Plan Project","award":["No.2024A0032"],"award-info":[{"award-number":["No.2024A0032"]}]},{"name":"Technology Health and Health Technology Plan Project in Nanchang City","award":["Grant No. 2025YLWS0001"],"award-info":[{"award-number":["Grant No. 2025YLWS0001"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute pancreatitis (AP) and Crohn\u2019s disease (CD) exhibit overlapping clinical presentations and an unexpectedly high rate of comorbidity. Whether this reflects shared genetic susceptibilities remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a cross-trait genome-wide association analysis leveraging European-ancestry summary statistics for AP (Ncases\u2009=\u20098446; Ncontrols\u2009=\u2009437,418) and CD (Ncases\u2009=\u200912,194; Ncontrols\u2009=\u200928,072). Firstly, cross-trait genetic correlation was estimated using linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL). Secondly, to pinpoint specific pleiotropic loci and prioritize candidate genes, we employed PLACO under a rigorous composite null hypothesis, integrated with Bayesian colocalization and SMR\/HEIDI analyses. Finally, we dissected the underlying biological context by mapping tissue-specific regulatory enrichment and pathway convergence using FUMA, MAGMA, and Stratified LD Score Regression (S-LDSC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      AP and CD showed significant positive genetic correlation (LDSC: r\n                      <jats:sub>g<\/jats:sub>\n                      \u2009=\u20090.178, SE\u2009=\u20090.079, P\u2009=\u20090.025; HDL: r\n                      <jats:sub>g<\/jats:sub>\n                      \u2009=\u20090.294, SE\u2009=\u20090.096, P\u2009=\u20090.0021). Pleiotropy analyses revealed 86 SNPs and 6 independent genome-wide significant pleiotropic loci (lead variants at 5q33.1, 6q22.33, 7q34, 10q24.2, 15q22.33 and 19q13.11, P\n                      <jats:sub>PLACO<\/jats:sub>\n                      \u2009&lt;\u20095\u2009\u00d7\u200910\n                      <jats:sup>\u22128<\/jats:sup>\n                      ). Colocalization showed suggestive evidence of a shared causal signal at 6q22.33 (PP4\u2009=\u20090.666). Gene-based tests of the AP-CD cross-trait statistics prioritized eight pleiotropic genes\u2014\n                      <jats:italic>RSPO3<\/jats:italic>\n                      ,\n                      <jats:italic>ATG16L1<\/jats:italic>\n                      ,\n                      <jats:italic>SMAD3<\/jats:italic>\n                      ,\n                      <jats:italic>FADS1<\/jats:italic>\n                      ,\n                      <jats:italic>ZPBP2<\/jats:italic>\n                      ,\n                      <jats:italic>FADS2<\/jats:italic>\n                      ,\n                      <jats:italic>PRKAA1<\/jats:italic>\n                      and\n                      <jats:italic>IRGM<\/jats:italic>\n                      . Gene-set analyses highlighted IL-23\/Th17-related and broader inflammatory response pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>AP and CD share polygenic susceptibility and converge on immune and inflammatory processes, with prioritized genes pointing to autophagy, lipid metabolism and TGF-\u03b2\/SMAD-related biology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0353031","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:29:36Z","timestamp":1789147776000},"page":"e0353031","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["From gut to pancreas: Shared genetic susceptibility and biological convergence in acute pancreatitis and Crohn\u2019s disease"],"prefix":"10.1371","volume":"21","author":[{"given":"Wenbin","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aocheng","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyi","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghui","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longxin","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5018-0212","authenticated-orcid":true,"given":"Chunyan","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"issue":"6","key":"pone.0353031.ref001","doi-asserted-by":"crossref","first-page":"549","DOI":"10.7861\/clinmed.2023-0493","article-title":"Crohn\u2019s disease: an update","volume":"23","author":"E Cockburn","year":"2023","journal-title":"Clin Med (Lond)"},{"issue":"2","key":"pone.0353031.ref002","doi-asserted-by":"crossref","DOI":"10.1136\/egastro-2023-100055","article-title":"Prebiotic selection influencing inflammatory bowel disease treatment outcomes: a review of the preclinical and clinical evidence","volume":"2","author":"A Ariaee","year":"2024","journal-title":"eGastroenterology"},{"issue":"1","key":"pone.0353031.ref003","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1186\/s12876-024-03481-8","article-title":"Global and regional burden of pancreatitis: epidemiological trends, risk factors, and projections to 2050 from the global burden of disease study 2021","volume":"24","author":"T Li","year":"2024","journal-title":"BMC Gastroenterol"},{"issue":"2","key":"pone.0353031.ref004","article-title":"Recent insights about autophagy in pancreatitis","volume":"2","author":"W-X Ding","year":"2024","journal-title":"eGastroenterology"},{"issue":"3","key":"pone.0353031.ref005","doi-asserted-by":"crossref","first-page":"276","DOI":"10.4291\/wjgp.v7.i3.276","article-title":"Pancreatic disorders in inflammatory bowel disease","volume":"7","author":"F Antonini","year":"2016","journal-title":"World J Gastrointest Pathophysiol"},{"issue":"2","key":"pone.0353031.ref006","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1080\/00365529950173096","article-title":"Risk of acute pancreatitis in patients with chronic inflammatory bowel disease. 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