Associations of cholecystectomy with the risk of gastroesophageal reflux disease: a Mendelian randomization study

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 × 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 – 4.09). At the same time, the analysis results of weighted median (OR = 2.30; 95% CI: 1.51 – 3.48) and weighted mode (OR = 2.21; 95% CI: 1.42 – 3.45) were also consistent with the direction of the IVW analysis and were statistically significant ( P < 0.05). Conclusions This study shows that patients who have undergone cholecystectomy are a susceptible population of GERD. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by National Key Clinical Specialty (General Surgery) of the First Affiliated Hospital of Wenzhou Medical University. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: In this study, we selected the Genome-wide association study（GWAS）summary statistics with the largest sample size from the public website "open GWAS"() 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". I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced are available online at