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 (ORIVW = 1.017, 95% CI (1.002,1.033), P= 0.03, Cochran’s Q= 7.8, p-value = 0.932, I2 = 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The ethical committee approved this study at the Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences (Research Approval Code: 28778 & Research Ethical Code: IR.SBMU.ENDOCRINE.REC.1400.084). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The original data used are publicly available at .