Inflammatory bowel disease increases the risk of pancreatitis: a two-sample bidirectional Mendelian randomization analysis

BMC Gastroenterol. 2025 Jan 11;25(1):13. doi: 10.1186/s12876-024-03571-7.

Abstract

Background: Previous studies have suggested an association between inflammatory bowel disease (IBD), and pancreatitis, including acute pancreatitis (AP) and chronic pancreatitis (CP). We aimed to examine the potential causal relationship between IBD and pancreatitis using the Mendelian randomization (MR) method.

Methods: We obtained data from genome-wide association studies (GWASs) in European individuals for IBD and its main subtypes, Crohn's disease (CD) and ulcerative colitis (UC) (31,665 IBD cases, 13,768 UC cases, 17,897 CD cases and 33,977 controls). Four independent summary statistics of pancreatitis from the the European Bioinformatics Institute (EMBL-EBI, 10,630 AP cases and 844,679 controls, 1,424 CP cases and 476,104 controls) and FinnGen Consortium (8,446 AP cases, 4,820 CP cases and 437,418 controls) were used for bidirectional MR analyses and sensitivity analysis. Finally, further meta-analysis was conducted on the MR results.

Results: Generally, IBD is associated with an increased risk of pancreatitis (IBD-AP, OR = 1.050, 95% CI 1.020-1.080, P = 7.20 × 10-5; IBD-CP, OR = 1.050, 95% CI 1.010-1.090, P = 0.019). In addition, UC increased the risk of pancreatitis (UC-AP, OR = 1.050, 95% CI 1.020-1.070, P = 9.10 × 10-5; UC-CP, OR = 1.090, 95% CI 1.040-1.140, P = 1.44 × 10-4) and CD increased the risk of acute pancreatitis (OR = 1.040, 95% CI 1.020-1.060, P = 9.61 × 10-5). However, no causal association was found between CD and the risk of chronic pancreatitis (P > 0.05). The reverse MR results showed that AP may be associated with a reduced risk of IBD and CD (AP-IBD, OR = 0.880, 95% CI 0.810-0.960, P = 0.003; AP-CD, OR = 0.830, 95% CI 0.730-0.940, P = 0.003). However, there is no causal relationship between AP and the risk of UC, and there is no causal relationship between CP and the risk of IBD and its subtypes(P > 0.05).

Conclusion: In conclusion, based on MR analysis and meta-analysis, our results showed a positive causal effect of IBD on pancreatitis, and subgroup analyses showed that UC and CD may promote the development of acute pancreatitis, whereas UC may promote the development of chronic pancreatitis. Reverse MR analysis suggests that AP may have a potential protective effect on IBD and CD.

Keywords: Acute pancreatitis; Chronic pancreatitis; Crohn's disease; Inflammatory bowel disease; Mendelian randomization; Ulcerative colitis.

Publication types

  • Meta-Analysis

MeSH terms

  • Colitis, Ulcerative* / complications
  • Colitis, Ulcerative* / genetics
  • Crohn Disease* / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Humans
  • Inflammatory Bowel Diseases / complications
  • Inflammatory Bowel Diseases / genetics
  • Mendelian Randomization Analysis*
  • Pancreatitis* / epidemiology
  • Pancreatitis* / etiology
  • Pancreatitis* / genetics
  • Pancreatitis, Chronic / epidemiology
  • Pancreatitis, Chronic / genetics
  • Polymorphism, Single Nucleotide
  • Risk Factors