The causal relationship between Graves’ disease and type 2 diabetes: Evidence from Bidirectional Mendelian Randomization Study

Introduction Numerous observational investigations have hinted at a possible link between Graves’ disease (GD) and the susceptibility to Type 2 diabetes (T2D). The primary objective of this study was to explore the potential underlying causal connection between GD and T2D through the application of bidirectional Mendelian randomization (MR) analysis. Materials and Methods MR analysis was conducted with summary-level data from genome-wide association studies (GWAS) for GD and T2D. Single-nucleotide polymorphisms (SNPs) for GD were extracted from 458,620 (1,678 cases and 456,942 controls) Europeans in the NBC Human Database, and the summary-level data of T2D (180,834 cases and 1,159,055 controls) were extracted from the DIAGRAM consortium. The primary analysis method was the inverse variance weighted (IVW) method. Heterogeneity and pleiotropy were considered to assess the causal relationship between GD and T2D. Sensitivity analyses were conducted to ensure the robustness of the findings. Results The initial analysis found no significant causal relationship between GD and an increased risk of T2D (OR = 1.019, 95% CI (0.997,1.042); SE = 0.01, P= 0.373). However, after sensitivity analyses and removal of outlier SNPs, a significant causal relationship was found (OR IVW = 1.017, 95% CI (1.002,1.033), P= 0.03, Cochran’s Q= 7.8, p-value = 0.932, I 2 = 0.0%). Conclusions The study indicates a causal link between GD and an elevated T2D risk, underscoring the need for blood sugar monitoring and specialized care for GD patients. Further research into GD-T2D mechanisms is essential for preventive strategies and interventions.