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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.
BMC Neurology
|August 14, 2026
Summary
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.
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