ABSTRACT
Background: Gallstone diseases and cholecystectomy are possibly associated with the severity of COVID-19 bidirectionally, yet the casual association remains unclear. Method: Applying genome-wide association study summary statistics of primarily European individuals, we utilized 2-sample Mendelian randomization to estimate the bidirectional causal effects of cholelithiasis, cholecystitis and cholecystectomy on three COVID-19 phenotypes: SARS-CoV-2 infection, COVID-19 hospitalization and severe COVID-19. Results: Inverse variance weighted Mendelian randomization results from the FinnGen consortium showed that none of cholelithiasis, cholecystitis and cholecystectomy was not causally associated with COVID-19 phenotypes, and vice versa. In addition, other methods including MR-Egger, weighted median, weight mode and simple mode exhibited approximate tendency as IVW. These results were all robust to sensitivity analysis. Conclusion: The forward MR analysis showed no causally significant impact of cholelithiasis, cholecystitis and cholecystectomy on COVID-19 phenotypes. Similarly, reverse MR results also showed no causal association between COVID-19 and cholelithiasis events.