Causal association between celiac disease and inflammatory bowel disease: A two-sample bidirectional Mendelian...

Area of Science:

• Gastroenterology
• Genetics
• Epidemiology

Background:

• Recent studies establish an epidemiological link between celiac disease (CeD) and inflammatory bowel disease (IBD).
• Understanding the causal relationship between CeD and IBD subtypes (ulcerative colitis [UC] and Crohn's disease [CD]) is crucial.

Purpose of the Study:

• To determine the causal relationship between celiac disease (CeD) and inflammatory bowel disease (IBD) using Mendelian randomization (MR).
• To investigate the genetic predisposition link between CeD and IBD subtypes, UC and CD.

Main Methods:

• Mendelian randomization (MR) analysis was performed using pooled genome-wide association study (GWAS) data.
• Inverse-variance-weighted approach, MR-Egger regression, weighted-mode, and weighted-median methods were employed.
• Sensitivity analyses included MR pleiotropy residual sum and outlier (MR-PRESSO) to ensure robustness.

Main Results:

• Genetic predisposition to CeD was associated with an increased risk of IBD (OR: 1.1408, P = 0.0003), UC (OR: 1.1646, P = 0.0012), and CD (OR: 1.1865, P = 3.07E-05).
• Reverse MR analysis indicated a genetic susceptibility link between IBD and CD with CeD.
• No significant genetic correlation was found between UC and CeD.

Conclusions:

• A bidirectional causal relationship exists between celiac disease (CeD) and inflammatory bowel disease (IBD), specifically Crohn's disease (CD).
• Ulcerative colitis (UC) shows a one-way causal link, augmenting the risk of developing CeD.
• Findings were validated across different GWAS databases, confirming the genetic associations.