Background This study aims to explore the causal relationships between inflammatory cytokines (ICs), metabolites, and the risk of arrhythmia through Mendelian Randomization (MR) analysis. Methods The causal associations were analyzed using five different MR analysis methods. Additionally, reverse MR analysis was performed to assess the impact of arrhythmias on these ICs and their metabolites. Results The MR analysis revealed that Oncostatin-M receptor (OSM) was significantly associated with an increased risk of arrhythmia (OR = 1.0812, p < 0.05), along with other ICs such as CXCL11 (OR = 1.0586), SIRT2 (OR = 1.0521), and FGF5 (OR = 1.0520). Five were positively correlated with arrhythmia risk, including X-22776 (OR = 1.071, p = 0.022) and tricosanoylsphingomyelin (OR = 1.066, p = 0.035).Mediation analysis demonstrated that FGF5 influences arrhythmia risk through its metabolite 1-palmitoyl-2-oleoyl-GPE, with a mediated effect accounting for 5.1% of the total effect. Conclusions Our findings suggest that specific ICs and metabolites contribute to the pathogenesis of arrhythmia. In particular, FGF5 and its metabolite 1-palmitoyl-2-oleoyl-GPE are implicated in increased arrhythmia risk, highlighting potential metabolic targets for therapeutic intervention.

The authors have declared no competing interest.

The author(s) received no specific funding for this work.

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