Protective effect of uridine on atrial fibrillation: a Mendelian randomisation study

Uridine, a pyrimidine nucleoside, is crucial in the synthesis of metabolites. According to observational studies, a higher plasma uridine level is associated with a lower risk of atrial fibrillation (AF). However, the casual relationship between uridine and AF is still unknown. In this study, we used the Mendelian randomisation (MR) approach to explore causality. Three genetic variants associated with uridine were identified from the Metabolomics GWAS server (7824 participants); summary-level datasets associated with AF were acquired from a genome-wide association study (GWAS) meta-analysis with 1,030,836 European participants (60,620 AF cases). We duplicated the MR analyses using datasets from AF HRC studies and the FinnGen Consortium, and then conducted a meta-analysis which combined the main results. The risk of AF was significantly associated with the genetically determined plasma uridine level (odds ratio [OR] 0.27; 95% confidence interval [CI] 0.16, 0.47; p = 2.39 × 10^-6). The association remained consistent in the meta-analysis of the various datasets (OR 0.27; 95% CI 0.17, 0.42; p = 1.34 × 10^-8). In conclusion, the plasma uridine level is inversely associated with the risk of AF. Raising the plasma uridine level may have prophylactic potential against AF.