Genetic Risk Factors in Autoimmune Thyroid Diseases: An Umbrella Review of Meta-Analyses and Evidence Credibility

Background Autoimmune thyroid diseases (AITDs) include Graves' disease and Hashimoto's thyroiditis, embodying a group of complex immune-regulated disorders characterized by a high degree of genetic predisposition. The results from various meta-analyses on AITD-related polymorphisms are still conflicting due to heterogeneity, population-specific effects, and the presence of poor-quality studies.MethodsThis umbrella review aims to merge and critically assess the findings from published meta-analyses to locate the valid genetic risk factors for AITDs. Meta-analyses published between 2005 and 2025 were accessed from databases and estimated using standard evidence-grading frameworks, including AMSTAR-2, GRADE, and the Venice criteria. Evidence was interpreted by integrating pooled effect estimates, heterogeneity, total sample sizes, and subgroup consistency.Results Among the assessed loci, TSHR polymorphisms yielded consistent associations with GD, supported by relatively large sample sizes, low heterogeneity, extensive study volume, and medium-to-high evidence certainty across study groups. CTLA-4 and PTPN22 variants showed heterogeneity-moderated associations with possible ethnicity-dependent effects. In contrast, FOXP3, cytokine genes, VDR, MTHFR, and TG polymorphisms showed unstable or low-certainty evidence, primarily due to high heterogeneity and fewer studies.Conclusion Thus, this study provides a hierarchical framework for interpreting genetic susceptibility in AITDs, helping to prioritize robust loci for functional validation and translational research.