Genetic association between autoimmune thyroiditis and microscopic polyangiitis: A two-sample Mendelian randomization study

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a group of life-threatening autoimmune small vessel vasculitis and the prognosis depends heavily on whether a prompt diagnosis is achieved. Autoimmune thyroiditis is the most common autoimmune endocrine disease and could overlap with other autoimmune diseases. It remains elusive whether autoimmune thyroiditis affects the risk of AAV development. We performed a 2-sample Mendelian randomization analysis to explore the true association between autoimmune thyroiditis and microscopic polyangiitis (MPA), a subtype of AAV. Independent single-nucleotide polymorphisms associated with Hashimoto thyroiditis or Grave disease with genome-wide significance were selected as instrumental variables from large genome-wide association study. MPA genome-wide association study summary statistics were obtained from FinnGen consortium. The inverse-variance weighted method was conducted as the primary analysis for estimating the effect of the exposure on the outcome. Mendelian randomization-Egger and the weighted median method were used to confirm the results. We found a causal association between Hashimoto thyroiditis and MPA while no causal effect of Grave disease on MPA. This study contributed a genetic viewpoint to the understanding of the link between autoimmune thyroiditis and AAV.