Association between type 1 diabetes mellitus and esophageal varices: a Mendelian randomization study

Abstract

Introduction: Esophageal varices (EV) are dilated submucosal veins in the distal esophagus connecting the portal vein to the systemic circulation. Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease associated with a variety of cardiovascular and peripheral vascular diseases. The aim of this study was to investigate the causal relationship between T1DM and EV from a genetic perspective. Material and methods: We performed a genome-wide association study of the causal relationship between T1DM and EV using pooled data from the GWAS database. Firstly, we conducted a two-sample Mendelian randomization (MR) study of these two diseases. Next, we used multivariate Mendelian randomization (MVMR) to further confirm the effect of type 1 diabetes on esophageal varices after excluding confounding factors such as cirrhosis and immune system disorders associated with type 1 diabetes mellitus. Sensitivity analyses were performed using Cochran’s Q test, MR-Egger intercept, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods, leave-one-out analysis and funnel plots. Results: In all two-sample MR analyses, the p-values of the IVW were all < 0.05. Meanwhile, the odds ratios (ORs) of both IVW and MR-Egger analyses were > 1, and the directions of the IVW and MR-Egger assays were consistent. No horizontal pleiotropy was found for the MR-Egger intercept, and leave-one out analysis showed that the results remained stable after the removal of individual SNPs. MVMR analysis showed that the causal relationship between type 1 diabetes mellitus and esophageal varices persisted after exclusion of immune-related confounders. Conclusions: The results of the MR analysis supported a causal relationship between T1DM and EV risk.