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Peer-reviewedCC BY 4.0PLOS One

From gut to pancreas: Shared genetic susceptibility and biological convergence in acute pancreatitis and Crohn’s disease

  • Wenbin Xu1
  • Aocheng Ji2
  • Lu Han3
  • Hao Xiong4
  • Yiyi Jin5
  • Wen Lin6
  • Yonghui Wu7
  • Yun Wang
  • Huan Zhong
  • Longxin Xiong
  • Chunyan Zeng
7 affiliations
  1. 1Department of Gastroenterology, Jiangxi Province Hospital of Integrated Chinese and Western Medicine (Central Hospital of Nanchang City), Nanchang, Jiangxi, China
  2. 2Department of Clinical Medicine, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China
  3. 3Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
  4. 4Postdoctoral Innovation Practice Base, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
  5. 5Eye Hospital of China Academy of Chinese Medical Sciences, Beijing, China
  6. 6Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada
  7. 7Department of General Surgery, Central Hospital of Nanchang City, Nanchang, Jiangxi, China
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Abstract

Background: Acute pancreatitis (AP) and Crohn’s disease (CD) exhibit overlapping clinical presentations and an unexpectedly high rate of comorbidity. Whether this reflects shared genetic susceptibilities remains unclear. Methods: We performed a cross-trait genome-wide association analysis leveraging European-ancestry summary statistics for AP (Ncases = 8446; Ncontrols = 437,418) and CD (Ncases = 12,194; Ncontrols = 28,072). 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). Results: AP and CD showed significant positive genetic correlation (LDSC: rg = 0.178, SE = 0.079, P = 0.025; HDL: rg = 0.294, SE = 0.096, P = 0.0021). 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, PPLACO < 5 × 10−8). Colocalization showed suggestive evidence of a shared causal signal at 6q22.33 (PP4 = 0.666). Gene-based tests of the AP-CD cross-trait statistics prioritized eight pleiotropic genes—RSPO3, ATG16L1, SMAD3, FADS1, ZPBP2, FADS2, PRKAA1 and IRGM. Gene-set analyses highlighted IL-23/Th17-related and broader inflammatory response pathways. Conclusions: AP and CD share polygenic susceptibility and converge on immune and inflammatory processes, with prioritized genes pointing to autophagy, lipid metabolism and TGF-β/SMAD-related biology.

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Cite

BibTeXRIS
BibTeX
@article{xu2026from,
  title = {{From gut to pancreas: Shared genetic susceptibility and biological convergence in acute pancreatitis and Crohn’s disease}},
  author = {Wenbin Xu and Aocheng Ji and Lu Han and Hao Xiong and Yiyi Jin and Wen Lin and Yonghui Wu and Yun Wang and Huan Zhong and Longxin Xiong and Chunyan Zeng},
  journal = {PLOS One},
  year = {2026},
  month = sep,
  doi = {10.1371/journal.pone.0353031},
  url = {https://doi.org/10.1371/journal.pone.0353031},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - From gut to pancreas: Shared genetic susceptibility and biological convergence in acute pancreatitis and Crohn’s disease
AU  - Wenbin Xu
AU  - Aocheng Ji
AU  - Lu Han
AU  - Hao Xiong
AU  - Yiyi Jin
AU  - Wen Lin
AU  - Yonghui Wu
AU  - Yun Wang
AU  - Huan Zhong
AU  - Longxin Xiong
AU  - Chunyan Zeng
PY  - 2026
DA  - 2026/09/11
JO  - PLOS One
DO  - 10.1371/journal.pone.0353031
UR  - https://doi.org/10.1371/journal.pone.0353031
AB  - Background: Acute pancreatitis (AP) and Crohn’s disease (CD) exhibit overlapping clinical presentations and an unexpectedly high rate of comorbidity. Whether this reflects shared genetic susceptibilities remains unclear. Methods: We performed a cross-trait genome-wide association analysis leveraging European-ancestry summary statistics for AP (Ncases = 8446; Ncontrols = 437,418) and CD (Ncases = 12,194; Ncontrols = 28,072). 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). Results: AP and CD showed significant positive genetic correlation (LDSC: rg = 0.178, SE = 0.079, P = 0.025; HDL: rg = 0.294, SE = 0.096, P = 0.0021). 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, PPLACO < 5 × 10−8). Colocalization showed suggestive evidence of a shared causal signal at 6q22.33 (PP4 = 0.666). Gene-based tests of the AP-CD cross-trait statistics prioritized eight pleiotropic genes—RSPO3, ATG16L1, SMAD3, FADS1, ZPBP2, FADS2, PRKAA1 and IRGM. Gene-set analyses highlighted IL-23/Th17-related and broader inflammatory response pathways. Conclusions: AP and CD share polygenic susceptibility and converge on immune and inflammatory processes, with prioritized genes pointing to autophagy, lipid metabolism and TGF-β/SMAD-related biology.
SN  - 1932-6203
ER  -