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Inflammatory bowel disease and celiac disease: A bidirectional Mendelian randomization study
Yue Shi1, Sijia Feng1, Mengdie Yan1
1Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Insights
This study found a two-way causal link between Crohn's disease (CD) and celiac disease (CeD), suggesting each condition can increase the risk of developing the other. Further research is needed to understand the interaction mechanisms between CD and CeD.
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.
Abstract:
Objective: Although previous epidemiological studies have reported substantial links between inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), and celiac disease (CeD), the causal relationship between the two remains unknown. The purpose of the current study was to evaluate the bidirectional causation between IBD and CeD using Mendelian randomization (MR). Method: We obtained genome-wide association study (GWAS) summary data of IBD (CD and UC) and CeD of thoroughly European ancestry from the IEU GWAS database. We screened eligible instrumental variables (IVs) according to the three assumptions of MR. MR was performed using MR-Egger, weighted median (WM), and inverse variance weighted (IVW) methods. The MR-Egger intercept and MR-PRESSO method investigated the horizontal pleiotropy effect. A leave-one-out analysis was performed to prevent bias caused by a single SNP. Results: The study assessed a bidirectional causal effect between CD and CeD; CD increased the risk of CeD (IVW odds ratio (OR) = 1.27, 95% confidence interval (CI) = 1.19-1.35, p = 3.75E-13) and vice-a-versa (IVW OR = 1.09, 95% CI = 1.05-1.13, p = 1.39E-05). Additionally, CeD was influenced by IBD (IVW OR = 1.24, 95% CI = 1.16-1.34, p = 9.42E-10) and UC (IVW OR = 0.90, 95% CI = 0.83-0.98, p = 0.017). However, we observed no evidence of a causal relationship between CeD and IBD (IVW OR = 1.00, 95% CI = 0.97-1.04, p = 0.900) or UC (IVW OR = 0.96, 95% CI = 0.92-1.02, p = 0.172). Conclusion: The present study revealed that IBD and CeD have a bidirectional causal relationship. However, it is slightly different from the results of previous observational studies, recommending that future studies focus on the mechanisms of interaction between CD and CeD.
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