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Inflammatory bowel disease and cardiovascular disease: A two-sample Mendelian randomization analysis
Kaiwen Wu1, Aoshuang Li1, Lei Liu2
1Department of Gastroenterology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China.
Insights
This study found no causal link between inflammatory bowel disease (IBD) and cardiovascular disease (CVD) risk. Mendelian randomization analysis did not support a significant association, contrasting with some observational findings.
Area of Science:
- Genetics
- Epidemiology
- Cardiovascular Health
Background:
- Observational studies suggest a link between inflammatory bowel disease (IBD) and cardiovascular disease (CVD) risk.
- However, a definitive causal relationship between IBD and CVD outcomes remains unestablished.
- This necessitates rigorous investigation into the potential causal pathways.
Purpose of the Study:
- To investigate the potential causal effect of inflammatory bowel disease (IBD) on cardiovascular disease (CVD) outcomes.
- To utilize a two-sample Mendelian randomization (MR) approach for robust causal inference.
- To clarify the etiological relationship between IBD and CVD.
Main Methods:
- A two-sample Mendelian randomization (MR) study was conducted using summary-level genome-wide association studies (GWAS) data from European populations.
- The inverse-variance weighted (IVW) method served as the primary analysis, complemented by MR Egger, weighted median, and MR-PRESSO.
- Extensive sensitivity analyses were performed to ensure the reliability and robustness of the findings.
Main Results:
- The primary IVW analysis revealed no statistically significant causal association between inflammatory bowel disease (IBD) and cardiovascular disease (CVD) outcomes (all P > 0.05).
- Complementary MR methods corroborated these findings, indicating a lack of causal effect.
- Sensitivity analyses detected no significant heterogeneity, pleiotropy, or outlier genetic variants, supporting the robustness of the results.
Conclusions:
- This Mendelian randomization study provides no evidence for a substantial causal effect of inflammatory bowel disease (IBD) on cardiovascular disease (CVD) risk.
- The findings contrast with previous observational reports, suggesting potential confounding factors or unmeasured biases in those studies.
- Further research is warranted to elucidate the mechanisms underlying the observed associations in epidemiological studies.
Background:
Although epidemiological studies have shown a positive relationship between inflammatory bowel disease (IBD) and risk of cardiovascular disease (CVD) outcomes, a solid causal relationship has not been established. Thus, a two-sample Mendelian randomization (MR) study was conducted to explore the potential causal effect between IBD and CVD outcomes.
Methods:
We performed a two-sample MR analysis to analyze the causal effect of the IBD on CVD outcome by using summary-level genome-wide association studies of European descent. The inverse-variance weighted (IVW) method was used as the main MR analysis, with complementary analyses of MR Egger, maximum likelihood, weighted median, penalized weighted media, simple mode, weighted mode, and MR-PRESSO methods. Multiple sensitivity analyses were used to evaluate the robustness of our results.
Results:
All P-values were greater than 0.05 in the IVW method, showing no evidence of a causal association between circulating IBD and CVD. Similar results were observed by using other MR methods. No evidence of heterogeneity, pleiotropy, or outlier single-nucleotide polymorphisms was detected. Sensitivity analyses demonstrated the robustness of the results.
Conclusion:
The findings of this study provided no evidence to support that IBD has a large effect on risk of CVD outcomes, which is in contrast to many previous observational reports. Further studies are needed to determine the potential mechanism of association identified in observational studies.
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