Bidirectional causal associations between Sjögren syndrome and gastrointestinal disorders: A two-sample Mendelian...

As a systemic autoimmune disorder, Sjögren syndrome (SS) often has symptoms related to the gastrointestinal manifestations. Nevertheless, the causal relationships between SS and gastrointestinal disorders remain incompletely understood. We implemented bidirectional Mendelian randomization (MR) framework to examine causal links between SS and 7 gastrointestinal diseases, including gastric ulcer (GU), duodenal ulcer (DU), irritable bowel syndrome (IBS), Crohn disease (CD), ulcerative colitis (UC), noninfectious gastroenteritis (NGE), and constipation (CP). The inverse-variance weighted approach served as the primary analytical tool while additional techniques used include MR-Egger, weighted median and weighted mode methods. Sensitivity analyses were carried out to determine if there was any evidence of pleiotropy and heterogeneity. Genetic liability for SS was linked with an increased risk of GU (odds ratio [OR] = 1.055, 95% CI = 1.013-1.100) and a reduced risk of IBS (OR = 0.970, 95% CI = 0.948-0.993). Reverse MR analysis indicated that NGE increases the risk of SS (OR = 1.347, 95% CI = 1.118-1.622). Causative relations were not shown between SS and DU, CD, UC, or CP. Sensitivity testing showed stability of the results. This MR analysis presents genetic evidence suggesting that SS increases the risk of GU and decreases the risk of IBS whereas NGE appears to increase the chance of having SS. No causative links with DU, CD, UC, and CP were discovered. These findings support the stratified gastrointestinal monitoring of SS and emphasize the importance of managing gut inflammatory processes within the context of reducing autoimmune risk. However, the protective effect of SS against IBS needs to be investigated.