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Mendelian randomization reveals the causal relationship between cholecystectomy and ischemic stroke
Yue Xiao1, Zejin Zhao1, Jinlong Liu2,3
1Department of Hepatobiliary Surgery, The Affiliated Hospital of Chengde Medical University, Chengde, Hebei, 067000, China.
Insights
Cholecystectomy (gallbladder removal) is not linked to overall ischemic stroke risk. However, genetic predisposition to cholecystectomy shows an inverse association with small-vessel ischemic stroke and possibly large-artery stroke.
Area of Science:
- Cardiovascular Science
- Genetics
- Epidemiology
Background:
- The relationship between cholecystectomy and ischemic stroke is not well-established.
- Investigating this association is crucial for understanding stroke risk factors.
Purpose of the Study:
- To examine the potential association between genetically predicted liability to cholecystectomy and ischemic stroke, including its subtypes.
- Utilizing Mendelian randomization (MR) to infer causality.
Main Methods:
- Employed Mendelian randomization (MR) with inverse variance weighted (IVW) as the primary method.
- Weighted median and MR-Egger regression were used for sensitivity analyses.
- Ischemic stroke subtypes were analyzed as secondary outcomes with Bonferroni correction.
Main Results:
- No significant association was found between genetically predicted cholecystectomy liability and overall ischemic stroke (P=0.208).
- A significant inverse association was observed with small-vessel ischemic stroke (P=0.009).
- A nominal inverse association with large-artery atherosclerotic ischemic stroke was suggested (P=0.023), but did not meet statistical significance after correction.
Conclusions:
- Genetically predicted cholecystectomy liability is not significantly associated with overall ischemic stroke.
- Evidence suggests an inverse association with small-vessel ischemic stroke and a potential inverse association with large-artery atherosclerotic ischemic stroke.
- No significant association was found for cardioembolic ischemic stroke.
Background:
The association between cholecystectomy and ischemic stroke remains unclear. Therefore, this study aimed to investigate the potential association of genetically predicted liability to cholecystectomy with ischemic stroke and its subtypes using Mendelian randomization (MR).
Methods:
The inverse variance weighted (IVW) method was used as the primary analytical method, with weighted median and MR-Egger regression as complementary methods. Overall ischemic stroke was defined as the primary outcome, whereas ischemic stroke subtypes were considered secondary outcomes. A Bonferroni-corrected significance threshold was applied to the three secondary outcomes. Heterogeneity, horizontal pleiotropy, and the influence of individual variants were assessed using sensitivity analyses.
Results:
Genetically predicted liability to cholecystectomy was not associated with overall ischemic stroke in the primary IVW analysis (OR = 0.57, 95% CI 0.23-1.37, P = 0.208). In the secondary analyses, the inverse association with small-vessel ischemic stroke remained significant after Bonferroni correction (OR = 0.10, 95% CI 0.02-0.57, P = 0.009). The inverse association with large-artery atherosclerotic ischemic stroke was nominally significant but did not meet the corrected threshold (OR = 0.09, 95% CI 0.01-0.71, P = 0.023), whereas no association was observed for cardioembolic ischemic stroke.
Conclusion:
Genetically predicted liability to cholecystectomy was not significantly associated with overall ischemic stroke. The secondary analyses supported an inverse association with small-vessel ischemic stroke and suggested a possible inverse association with large-artery atherosclerotic ischemic stroke. No significant association was observed for cardioembolic ischemic stroke.
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