Blood Metabolome Mediates the Effect of the Plasma Lipidome on the Risk of Atrial Fibrillation: A Mendelian Randomization Study
Year: 2025
Type: article
Study design: Observational Study
Abstract: 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.
Source: Clinical Cardiology
DOI: 10.1002/clc.70112
Authors: Yanglulu Su, Yi Ning, Zhiyuan Jiang, Guoqiang Zhong
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,810
OpenAlex ID: W4408246299