Mediating role of blood metabolites in the relationship between arrhythmia and hyperthyroidism in East Asian populations.

BACKGROUND AND AIM: Arrhythmia is a common manifestation of hyperthyroidism, and blood metabolites may play a regulatory role in cardiovascular health and thyroid function. However, the mediating role of blood metabolites between arrhythmia and hyperthyroidism, particularly in East Asian populations, remains unclear.

METHODS AND

RESULTS

We used large-scale GWAS data from East Asian populations for a two-step Mendelian randomization (MR) analysis. First, we assessed the causal link between arrhythmia and hyperthyroidism, then evaluated the mediating role of blood metabolites. GWAS data on arrhythmia, hyperthyroidism, and metabolites were used. Mediation effects were calculated, and sensitivity analyses ensured robustness. The inverse-variance weighted (IVW) method was the primary tool, while colocalization analysis assessed shared genetic loci, confirming if the genetic signals for these traits arise from the same variants. The analysis revealed a significant association between arrhythmia and increased hyperthyroidism risk (OR = 1.272, p = 0.003), and reverse MR confirmed a positive association (OR = 1.039, p = 0.036), indicating a bidirectional link. Sensitivity analyses using weighted median, simple mode, and weighted mode provided consistent results. Blood urea nitrogen was identified as a key mediator, explaining 9.7 % of the causal relationship between arrhythmia and hyperthyroidism. These findings were unaffected by heterogeneity or pleiotropy.

CONCLUSIONS

Blood urea nitrogen is a novel mediator in the arrhythmia-hyperthyroidism relationship, highlighting its potential role in cardiovascular and thyroid health.