Causal role of peripheral immunity in gastroduodenal diseases: A Mendelian randomization study and meta-analysis

Background : Peripheral immune cells have important roles in upper digestive system diseases. In this meta-analysis, we explored causal relationships between three upper digestive system diseases and peripheral immune cells. Methods : Genetic summary statistics were collected from an open genome-wide association study database. Causal relationships between seven peripheral immune cell types and gastric ulcer, duodenal ulcer, and chronic gastritis conditions were evaluated using double-sample bidirectional Mendelian Randomization. Cochran's Q and Mendelian random-Egger regression tests were used to evaluate heterogeneity and pleiotropy. A meta-analysis improved the statistical efficiency of our results. Results : We observed a positive correlation between B cells, T cell maturation stages, and Tregs with the upper digestive system (odds ratio [OR]:1.0199, 95% confidence interval [CI]: 0.9604–1.0611; OR: 1.0006, 95% CI: 0.9997–1.0015; and OR: 1.0008, 95% CI: 1.0003–1.0014, respectively). By contrast cDCs, myeloid cells, and TBNKs were negatively correlated with the upper digestive system (OR: 0.9635, 95% CI: 0.8923–1.0403; OR: 0.9991, 95% CI: 0.9986–0.9997; and OR: 0.9740, 95% CI: 0.9199–1.0312, respectively). Conclusions : We observed cause-and-effect relationships between genetically predicted peripheral immune cells and upper digestive diseases. These findings suggest peripheral immune cell monitoring and improved guidelines for the risk management of upper digestive diseases.