Use of Bidirectional Mendelian Randomization to Unveil the Association of Infection and Autoimmune Thyroid Diseases

Previous observational studies found associations between infection and autoimmune thyroid diseases (AITDs), but the causal nature of this association is still uncertain. We investigated the causal effect of six crucial antibodies against on AITDs using a bidirectional Mendelian randomization (MR). We found that anti- outer membrane protein (OMP) significantly increased the risk of hyperthyroidism and Graves' disease (GD). In addition, our reverse MR analysis indicated that hyperthyroidism could increase the levels of cytotoxin-associated gene A and OMP antibodies. We also observed causal roles of GD on anti- OMP. Our analyses indicate the mutual effects of infection and AITDs, suggesting the existence of a gut-thyroid axis. These results also provide evidence of the bidirectional causal association between anti- OMP with hyperthyroidism and GD, resulting in a vicious circle.