Abstract Background: Cholecystectomy is the standard surgery for patients with gallbladder disease, but the impact of cholecystectomy on gastroesophageal reflux (GERD) is not clear. Methods: We obtained genetic variants associated with cholecystectomy at a genome-wide significant level (P value < 5 [mult] 10-8) as instrumental variables (IVs) and performed Mendelian randomization (MR) to explore the relationship with GERD. Results: The Inverse Variance Weighted analysis (IVW) showed that the risk of GERD in patients after cholecystectomy increased (OR = 2.19; 95% CI: 1.18 [ndash] 4.09). At the same time, the analysis results of weighted median (OR = 2.30; 95% CI: 1.51 [ndash] 3.48) and weighted mode (OR = 2.21; 95% CI: 1.42 [ndash] 3.45) were also consistent with the direction of the IVW analysis and were statistically significant (P [lt] 0.05). Conclusions: This study shows that patients who have undergone cholecystectomy are a susceptible population of GERD. Keywords: Cholecystectomy; Gastroesophageal; Mendelian randomization.

The authors have declared no competing interest.

This work was supported by National Key Clinical Specialty (General Surgery) of the First Affiliated Hospital of Wenzhou Medical University.

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In this study, we selected the Genome-wide association study（GWAS）summary statistics with the largest sample size from the public website "open GWAS"(https://gwas.mrcieu.ac.uk/) developed by the MRC Integrative Epidemiology Unit (IEU) at the University of Bristol. The GWAS ID of cholecystectomy is "ukb-b-6235". The GWAS ID of GERD is "ebi-a-GCST90000514".

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