Genetically predicted plasma metabolites mediate the causal role of immune cells in atrial fibrillation

OBJECTIVE: Determining and measuring the possible mediating function of plasma metabolites in the causative link between immunophenotype and atrial fibrillation (AF). METHODS: A bi-directional two-sample Mendelian randomization (MR) analysis of 731 immune cell phenotypes and atrial fibrillation was conducted using summary-level data from a genome-wide association study (GWAS). Subsequent investigations centered on examining 1400 plasma metabolites for potential mediating roles in immune cell-induced atrial fibrillation using two-step MR. RESULTS: After screening 29 immune cells linked to AF risk, this study found that 15 of them were linked to an increased risk of AF and 14 to a lower risk. Furthermore, a possible causal link between 22 plasma metabolites and atrial fibrillation was found. Five immune cell-metabolite matches were ultimately shown to have mediating functions in the pathology of atrial fibrillation. Of the five final sets of data, one group showed a partial mediation effect, two metabolites and one metabolite ratio showed suppression effects of moderating the process of immune cell-caused atrial fibrillation. CONCLUSION: The results point to a potential major role for immune cells and plasma metabolites in the initiation and progression of AF. For the purpose of preventing and treating AF, these findings could offer novel biomarkers or therapeutic targets in the unclarified pathogenesis of atrial fibrillation, particularly for immune-related pathways.