Causal associations between type 2 diabetes mellitus and chronic hepatitis C: A bidirectional Mendelian randomization study of East Asians

Abstract Observational studies have shown a bidirectional relationship between type 2 diabetes mellitus (T2DM) and chronic hepatitis C (CHC). However, the causal relationship remains unknown. We explored the connection between T2DM and CHC in East Asians utilizing Mendelian randomization (MR). Two-sample bidirectional MR was applied to summarized statistics from genome-wide association studies. The inverse variance-weighted method, weighted-median method, MR-Egger regression, weighted mode, simple mode, heterogeneity test, pleiotropy test, and MR-PRESSO were employed for MR analysis. Results of various methods revealed an inverse relationship between T2DM and CHC, with an odds ratio (OR) (95% confidence interval [CI]) of 0.906 (0.858–0.957; P=0.00037), 0.825 (0.732–0.931; P=0.0025), 0.882 (0.808–0.962; P=0.00484), and 0.862 (0.772–0.961; P=0.00922) from inverse variance-weighted, MR-Egger, weighted median, and weighted mode, respectively. Further, no heterogeneity or directional pleiotropy was identified in Cochran’s Q test and Egger’s intercept. In the backward MR analysis, the P-values were all not statistically significant, indicating no detectable connection between CHC and T2DM. Finally, there was no proof of a connection involving blood sugar levels, hemoglobin A1c levels, and CHC risk. This large MR analysis revealed that T2DM had an inverse relationship with CHC, while CHC had no causality with T2DM.