Causal Relationship Between Emotional Disorders and Thyroid Disorders: A Bidirectional Two-Sample Mendelian Randomization Study

Introduction: The interplay between emotional disorders and thyroid disorders has been subject to numerous observational studies, which have consistently reported associations but have failed to establish clear causal links due to the multifactorial etiology and influences. We conducted a bidirectional two-sample Mendelian randomization (MR) analysis to explore the genetic causal association between emotional disorders and thyroid disorders.

Methods: We employed several methods, including inverse-variance weighted (IVW), weighted median, weighted mode, and MR Egger regression. Additionally, sensitivity analyses were conducted using MR-Egger, MR Pleiotropy Residual Sum and Outlier (MR-PRESSO), Cochran's Q, and leave-one-out methods.

Results: IVW results showed negative causal relationships between bidirectional emotional disorders and hypothyroidism, toxic single thyroid nodules in thyrotoxicosis, and hyperthyroidism/toxicity. Additionally, there was a positive causal relationship between anxiety disorders and hypothyroidism. IVW results of reverse MR analysis estimates revealed a positive causal relationship between hypothyroidism, autoimmune thyroiditis, and recurrent or chronic depression. Additionally, there was a negative causal relationship between hyperthyroidism/toxicity and bipolar disorder.

Conclusion: This bidirectional two-sample MR study preliminarily reveals a complex, bidirectional causal relationship between emotional disorders and thyroid disorders, particularly highlighting the role of thyroid dysfunction in the development of certain emotional disorders and vice versa.