Blood Metabolome Mediates the Effect of the Plasma Lipidome on the Risk of Atrial Fibrillation: A Mendelian Randomization Study

Background and Objective

Atrial fibrillation (AF), a common arrhythmic disorder, is increasing in prevalence annually and has become an important public health problem that jeopardizes human health. Metabolites are small molecules produced in the process of metabolic reactions, and they can affect the risk of disease and possibly become targets for disease management.

Methods

We used two-sample and bidirectional MR to explore potential causal associations between lipid groups and AF. Two-step MR analysis was used to explore whether plasma metabolites mediated a causal effect from lipidomes to AF.

Result

We assessed the effect of 179 lipids on AF using IVW models and observed that 8 lipids were associated significantly with AF (p < 0.05). Likewise, we assessed the effect of 1091 metabolites and 309 metabolite ratios on AF and observed that 22 metabolites were significantly associated with AF (p < 0.05). We analyzed the blood metabolites above as mediators in the pathway from the lipidomes above to AF. We found that levels. Of lipid sterol ester (27:1/18:3) were associated with lower homoarginine levels, and lower metabolite homoarginine levels were associated with an increased risk of AF.

Conclusion

Our study identified a causal relationship between plasma liposomes and AF, and additionally found that the plasma metabolite homoarginine levels can act as a mediator of the lipid sterol ester in its effect on AF.