Mendelian randomization study of inflammatory bowel disease and type 1 diabetes

Endocrine. 2024 Dec;86(3):943-953. doi: 10.1007/s12020-024-03919-9. Epub 2024 Jul 31.

Abstract

Purpose: Our purpose was to investigate and test the causal relationship between type 1 diabetes (T1D) and inflammatory bowel disease (IBD) and its major phenotypes, including ulcerative colitis (UC) and Crohn's disease (CD), in two large datasets.

Methods: We obtained IBD samples from the largest publicly available genome-wide association study (GWAS), as well as the FinnGen database and the publicly accessible IEU GWAS database of T1D. We employed a two-sample Mendelian randomization approach to assess bidirectional causality using the inverse variance weighting (IVW) method as the primary outcome.

Results: Genetic predisposition to T1D was associated with reduced risk of IBD (IVW: odds ratio (OR), 0.867; 95% confidence interval (CI), [0.852, 0.883]; P < 0.001), UC (OR = 0.879 [0.823, 0.939], P < 0.001), and CD (OR = 0.925 [0.872, 0.981], P = 0.009). The republication results found IBD genetically possessed negative association with T1D (OR = 0.781 [0.684, 0.891], P < 0.001). Additionally, a meta-analysis of results was conducted to prove the strong evidence between T1D and CD (OR = 0.95 [0.91, 0.98]; p = 0.01).

Conclusions: This study first demonstrated a causal effect of TID on the reduced risk of CD in the mendelian randomization study.

Keywords: Crohn’s disease; Two-sample Mendelian randomization; Type 1 diabetes; Ulcerative colitis.

MeSH terms

  • Colitis, Ulcerative / epidemiology
  • Colitis, Ulcerative / genetics
  • Crohn Disease / epidemiology
  • Crohn Disease / genetics
  • Diabetes Mellitus, Type 1* / epidemiology
  • Diabetes Mellitus, Type 1* / genetics
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Humans
  • Inflammatory Bowel Diseases* / epidemiology
  • Inflammatory Bowel Diseases* / genetics
  • Mendelian Randomization Analysis*
  • Polymorphism, Single Nucleotide