Causal relationship between Hashimoto's thyroiditis and non-ischemic cardiomyopathy and the mediating role of inflammatory cytokines: Evidence from genetic association analysis

Background: Previous studies report that Hashimoto's thyroiditis (HT) may be associated with non-ischemic cardiomyopathy (NICM); However, the causal relationship remains to be elucidated. Here, we aimed to investigate the causal relationship between HT and NICM through Mendelian randomization (MR) and explore the potential mediating role of inflammatory cytokines within this association.

Methods: The bidirectional two-sample MR, multivariable MR and mediation MR analyses were conducted based on genome-wide association study summary datasets, and MR results were further supported by multiple sensitivity analysis methods.

Results: We presented genetic evidence that HT could unidirectionally increase the risk of NICM (odds ratios [OR]: 1.09, 95 % confidence intervals [CI]: 1.03-1.15, P = 0.001). After adjusting for multiple potential cardiovascular risk factors such as body mass index, hypertension, blood glucose levels, several dyslipidemias, alcohol consumption, heart valve problem, thyroid function, heart rate and arrhythmia, the causal effect of HT on NICM remained statistically significant. Further mediation MR analysis results showed that monokine induced by gamma interferon (MIG) could act as a mediator (OR = 1.026, 95 % CI = 1.006-1.052), accounting for about 28.8 % of the increased risk of NICM in patients with HT.

Conclusions: Our study proposes a causal relationship between HT and NICM, as well as the mediating role of MIG in this process, highlighting the importance of evaluating myocardial damage in patients with HT and providing new insights into the targeted treatment for high-risk patients.