{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:52:22Z","timestamp":1790272342470,"version":"4.1.0"},"reference-count":61,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":211,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270667"],"award-info":[{"award-number":["82270667"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U23A20492"],"award-info":[{"award-number":["U23A20492"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8217033803"],"award-info":[{"award-number":["8217033803"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170559"],"award-info":[{"award-number":["82170559"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2025JJ40083"],"award-info":[{"award-number":["2025JJ40083"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Changsha","award":["kq2502174"],"award-info":[{"award-number":["kq2502174"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Obesity is recognized as a prominent contributing factor for pancreatic diseases; however, the mechanisms remain elusive. We aimed to identify the mediating role of circulating proteins in these associations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A two-step Mendelian randomization (MR) was conducted to investigate associations between nine obesity indicators, thousands of circulating proteins, with three pancreatic diseases (acute pancreatitis, chronic pancreatitis, and pancreatic carcinoma). Colocalization analyses were performed to validate these associations. Protein mediating networks among obesity indicators and pancreatic diseases were investigated by mediation analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Genetically predicted circulating levels of 4, 2, and 2 proteins were associated with acute pancreatitis, chronic pancreatitis, and pancreatic carcinoma, respectively. In mediation analysis, decreased chymotrypsin B2 (CTRB2) levels mediated 1.03% (95% CI [confidence interval] 0.02%\u20132.03%) of the effects of body mass index on acute pancreatitis. Increased R-spondin 3 (RSPO3) levels mediated the effects of body mass index (2.95%, 95% CI 0.18%\u20135.73%), body fat percentage (4.53%, 95% CI 1.11%\u20137.96%), waist\u2013hip ratio (8.48%, 95% CI 3.11%\u201313.86%), and visceral adipose tissue (3.93%, 95% CI 0.64%\u20137.22%) on acute pancreatitis. We also found increased klotho beta (KLOTB) levels mediated the effects of waist\u2013hip ratio (7.01%, 95% CI 3.30%\u201310.71%) and visceral adipose tissue (8.98%, 95% CI 4.55%\u201313.41%) on chronic pancreatitis, and decreased receptor tyrosine kinase-like orphan receptor 1 (ROR1) levels mediated the effects of body mass index (10.39%, 95% CI 3.36%\u201317.42%) and visceral adipose tissue (6.29%, 95% CI 1.00%\u201311.58%) on pancreatic carcinoma.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The MR suggests that circulating CTRB2, RSPO3, KLOTB, and ROR1 proteins may mediate associations between obesity and pancreatic diseases.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/gastro\/goaf057","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T19:58:52Z","timestamp":1753991932000},"source":"Crossref","is-referenced-by-count":1,"title":["Unveiling CTRB2, RSPO3, KLOTB, and ROR1 as obesity-pancreatic disease association proteins: a comprehensive Mendelian randomization study"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2351-578X","authenticated-orcid":false,"given":"Chunhua","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, P. 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R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5858-6225","authenticated-orcid":false,"given":"Yao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5055-5627","authenticated-orcid":false,"given":"Shuai","family":"Yuan","sequence":"additional","affiliation":[{"name":"Institute of Environmental Medicine, Karolinska Institutet , Stockholm,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6880-2577","authenticated-orcid":false,"given":"Xue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Big Data in Health Science, School of Public Health and The Second Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6623-6839","authenticated-orcid":false,"given":"Jie","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8376-3481","authenticated-orcid":false,"given":"Xiaocang","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital , Tianjin, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4029-4192","authenticated-orcid":false,"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Postdoctoral Station of Clinical Medicine, The Third Xiangya Hospital, Central South University , Changsha, P. R.","place":["China"]},{"name":"Xiangya School of Public Health, Central South University , 138 Tongzipo Road , Changsha, Hunan 410013,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7281-1078","authenticated-orcid":false,"given":"Xiaoyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The Third Xiangya Hospital, Central South University , Changsha, P. 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