Exploration of the relationships between immune cells, metabolic mediators, and atrial fibrillation: A bidirectional Mendelian randomization study

Studies have shown a close correlation among immune cells, plasma metabolites, and atrial fibrillation (AF). However, it is not clear if this association is related, which we used Mendelian randomization (MR) to investigate. We analyzed the association between immune cells, plasma metabolites, and AF by using summarized data from genome-wide association studies. Among them, we explored the associations between immune cells and AF by using bidirectional MR analysis. Combined with mediation analysis and multivariable MR, we further identified potential mediating plasmic metabolites. Results shows that causal relationships between 8 immune cell phenotypes and AF were identified with all 8 exhibiting reverse causality. Furthermore, 22 plasma metabolites have a causal relationship with AF. In addition, 2 immune cell phenotypes including CD25 on IgD + CD38dim and CX3CR1 on CD14 + CD16-monocyte, which were found to have causal relationships with 4 plasma metabolites, including 4-acetamidobutanoate levels, Octadecanedioylcarnitine (C18-DC) levels, Linolenate [alpha or gamma; (18:3n3 or 6)] levels, and N-acetyl-aspartyl-glutamate levels, which might be mediators. Ultimately, only 4-acetamidobutanoate levels, CD25 on IgD + CD38dim, and AF did appear to function as mediators (P-value = .030 < .05). In conclusion, immune cells and plasma metabolites are causally associated with AF. We have identified that 4-acetamidobutanoate levels appear to mediate the pathway linking CD25 on IgD + CD38dim to AF. This finding provides a new perspective for the early prevention and diagnosis of preatrial AF.