The genetic association between celiac disease and risk of functional dyspepsia: A Mendelian randomization study

Celiac disease (CeD) is a common autoimmune disease of the small intestine triggered by ingesting gluten-containing foods. Chronic symptoms are characteristic of functional dyspepsia (FD), including chronic epigastric pain and burning. The clinical and genetic overlap between FD and CeD is currently being investigated in a large-scale comorbidity and genetic predisposition study. In this study, causal connections between CeD and FD were evaluated using Mendelian randomization (MR) methods, including the inverse variance weighted, MR-Egger regression, and the weighted median methods. Cochran Q test was used to examine heterogeneity among the causal effects. MR-Egger regression indicates the average pleiotropic effect of instrumental variables. MR pleiotropy residual sum and outlier analysis was conducted to detect outlier instruments and remove pleiotropy. CeD was associated with a modestly increased risk of FD, with an estimated effect size of 3.2% (odds ratio = 1.032 [1.008-1.056], P = .019). The reverse MR analysis provided no significant evidence supporting a causal effect of FD on CeD risk (odds ratio = 1.173 [0.989-1.390], P = .099). In addition, no substantial heterogeneity or horizontal pleiotropy was detected in either the forward or reverse MR analyses. These findings highlight the need for routine FD screening among patients with CeD and indicate that optimizing CeD management may help reduce the burden of FD in this population.