Inflammatory bowel disease and celiac disease: A bidirectional Mendelian randomization study

Area of Science:

• Gastroenterology
• Genetics
• Epidemiology

Background:

• Observational studies suggest links between inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), and celiac disease (CeD).
• The causal relationship between IBD and CeD remains unclear, necessitating further investigation.

Purpose of the Study:

• To evaluate the bidirectional causation between IBD (CD and UC) and CeD using Mendelian randomization (MR).
• To clarify the etiological relationship between these gastrointestinal conditions.

Main Methods:

• Utilized genome-wide association study (GWAS) summary data for IBD (CD, UC) and CeD from European ancestry populations.
• Applied MR methods (MR-Egger, weighted median, inverse variance weighted) with instrumental variables selected based on MR assumptions.
• Assessed horizontal pleiotropy using MR-Egger intercept and MR-PRESSO, and performed leave-one-out analysis to ensure robustness.

Main Results:

• Confirmed a bidirectional causal effect between Crohn's disease (CD) and celiac disease (CeD).
• CD significantly increased the risk of CeD (OR=1.27), and CeD increased the risk of CD (OR=1.09).
• CeD was influenced by IBD (OR=1.24) and UC (OR=0.90), but no causal relationship was found between CeD and overall IBD or UC alone.

Conclusions:

• Inflammatory bowel disease (IBD) and celiac disease (CeD) exhibit a bidirectional causal relationship.
• Findings differ from some previous observational studies, highlighting the need for research into the specific interaction mechanisms between CD and CeD.