Causal association between helicobacter Pylori infection and Sjogren’s syndrome: a bi-directional Mendelian randomization analysis

Abstract Background: Based on the results of existing observational studies, it can be found that there is a potential link between Helicobacter pylori(H.pylori) infection and Sjogren’s syndrome(SS), but the causal relationshipbetween them remains unknown. This study applied Mendelian randomization (MR) to evaluate the causal relationship between H.pylori infection and SS. Method: In this study, genome-wide association studies (GWAS) summary statistics on H.pylori infection [sample size=8735 (EBI)] and SS [sample size=368,028 (cases=2495, controls=365533) (FinnGen)] were used. we used bi-directional MR to evaluate the association between H.pylori infection and SS for identifying causation. The major analysis method of MR was performed using inverse-variance weighted(IVW), supplemented by MR-Egger and the weighted median approaches. In addition, the stability and reliability of the results were tested using the retention method, heterogeneity test, and horizontal gene pleiotropy test. Results: The evidence of the impact of H.pylori infection on SS risk was found in IVW results[odds ratio (OR)=1.6705; 95% confdence interval (CI)=1.0966 to 2.5446; P=0.0168]. Similarly, the evidence of the impact of SS on H.pylori infection risk has also been found(OR=1.0158; 95%CI=1.0033 to 1.0285; P=0.0128). Conclusion: The results of MR analysis support that H.pylori infection was causally associated with SS, and SS can lead to a higher risk of H.pylori infection.We want to provide novel approaches for continued H.pylori and SS-related research and therapy by evaluating the genetic relationship between H.pylori infection and SS.