Causal relationship between graves’ disease and mental disorders: A bidirectional Mendelian randomization study

Objective

Many patients with Graves' disease (GD) also suffer from mental disorders in clinical practice, but their causal relationship remains unclear. This study aims to investigate the causal relationship between GD and common mental disorders using a bidirectional Mendelian randomization (MR)approach.

Methods

We derived genome-wide association study (GWAS) data for common mental disorders, including major depressive disorder (MDD), anxiety disorders, bipolar disorder, and attention-deficit/hyperactivity disorder (ADHD), from the Psychiatric Genomics Consortium consortium. GWAS data for GD were obtained from the FinnGen consortium. Subsequently, a bidirectional MR analysis was conducted, with the inverse-variance weighted (IVW) methods as the primary MR analysis method. Sensitivity analysis used Cochran's Q test, MR-Egger intercept test, and leave-one-out method.

Results

IVW results in MR demonstrated a positive association between genetic susceptibility to GD and bipolar disorder (OR = 1.073, 95 % CI: 1.042–1.105, p = 2.882 × 10⁻⁶). Similar causal estimates were obtained through MR-Egger regression and the weighted median method. Additionally, both Cochran's Q test and MR-Egger intercept test indicated no evidence of heterogeneity or pleiotropy. However, no causal associations were demonstrated between GD and MDD, anxiety disorders, or ADHD. Furthermore, a causal relationship between genetic susceptibility to common mental disorders and GD was not evidenced.

Conclusions

This bidirectional MR study supports the role of GD in the causal association with an increased risk of bipolar disorder, which guides us to pay attention to the mental diseases of GD patients in the clinic.