Identifying the Genetic Associations Between Diabetes Mellitus and the Risk of Vitiligo

Purpose: While increasing observational studies have suggested an association between diabetes mellitus (DM) and vitiligo, the causal relationship and possible mechanism remain unclear. Methods: Publicly accessible genome-wide association study (GWAS) was utilized to conduct a bidirectional two-sample Mendelian randomization (MR) analysis. GWAS data for diabetes and vitiligo were obtained from the UK Biobank Consortium (20203 cases and 388756 controls) and the current GWAS data with largest cases (GCST004785, 4680 cases and 39586 controls) for preliminary analysis, respectively. Inverse variance weighting (IVW) was used as the main analysis method. Several sensitivity analyses were utilized to test the pleiotropy or heterogeneity. To explore the possible mechanism of gene-generating effects represented by the final instrumental variables in the analysis, enrichment analysis was conducted using the DAVID and STRING database. Results: IVW method showed a significant genetic causal association between DM and vitiligo (OR = 1.20, 95% CI: 1.08-1.33, PIVW = 0.0009). Diabetes subtype analysis showed that T2D (type 2 diabetes) were associated with an increased risk of vitiligo (OR = 1.13, 95% CI: 1.00-1.27, PIVW = 0.0432). Sensitivity analysis further confirmed the robustness of the results. The enrichment analysis revealed that the genetic inducing effects of diabetes mellitus on vitiligo were primarily about pancreatic secretion and protein digestion and absorption pathway. Conclusion: Our findings provide genetic evidence that there is a notable association between T2D and an elevated risk of vitiligo in European populations. This result may explain why the co-presentation of T2D and vitiligo is often seen in observational studies, and emphasize the significance of vigilant monitoring and clinical evaluations for vitiligo in individuals diagnosed with T2D. The aberrant glucose and lipid metabolism and the primary nutrient absorption disorder of vitiligo brought on by diabetes may be the potential mechanisms behind this association.