Unraveling the genetic association between autoimmune thyroid diseases and idiopathic inflammatory myopathies in the European population

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While clinical observations suggest potential links between thyroid autoimmunity disorders (specifically Hashimoto thyroiditis and Graves' disease) and idiopathic inflammatory myopathies (notably dermatomyositis and polymyositis), the underlying causative mechanisms remain incompletely understood. We implemented a Mendelian randomization approach to elucidate potential causal pathways through which thyroid autoimmunity might influence the development of idiopathic inflammatory myopathies. Comprehensive genetic association data regarding thyroid autoimmunity and idiopathic inflammatory myopathies were obtained through systematic extraction from IEU openGWAS project and FinnGen biobank repositories. We identified genetic instruments using stringent selection criteria (P < 5 × 10-8, r2 < 0.01, and kb = 10,000) to ensure robust genetic associations. Statistical analyses incorporated multiple complementary approaches, primarily utilizing inverse variance weighted estimation, supplemented by comprehensive sensitivity assessments to validate findings robustness. Genetic instrumental variable analyses revealed that individuals with Hashimoto thyroiditis exhibited significantly elevated susceptibility to both dermatomyositis (odds ratio [OR]: 1.625, 95% confidence interval [CI]: 1.056-2.502, P = .027) and polymyositis (OR: 2.248, 95% CI: 1.116-4.528, P = .023). Further analyses demonstrated that Graves' disease significantly influenced the development of idiopathic inflammatory myopathies, showing substantial associations with both dermatomyositis (OR: 1.484, 95% CI: 1.184-1.861, P < .001) and polymyositis (OR: 1.530, 95% CI: 1.152-2.032, P = .003). Multiple sensitivity analyses, including pleiotropy assessments and heterogeneity evaluations, confirmed the stability and reliability of these findings. Our comprehensive genetic analysis establishes robust evidence for causative pathways linking thyroid autoimmunity with the subsequent development of idiopathic inflammatory myopathies, suggesting shared pathogenic mechanisms between these conditions.

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