Possible Protective Effects of Uridine on Atrial Fibrillation: A Mendelian Randomization Study

Abstract Uridine, a pyrimidine nucleoside, plays a crucial role in the synthesis of metabolites. According to recent research, higher plasma uridine levels are associated with a lower risk of atrial fibrillation (AF). However, the casual inference between uridine and AF is still unknown. In this study, we used the Mendelian randomization (MR) approach to elucidate possible causality. Three genetic variants associated with uridine were identified from the Metabolomics GWAS server (7,824 participants); summary-level datasets associated with AF were acquired from a genome-wide association study (GWAS) meta-analysis containing 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 conducted a meta-analysis to combine the main results. The incidence of AF was incidentally associated with a one standard deviation increase in genetically determined plasma uridine [odds ratio (OR), 0.27; 95% confidence interval (CI), 0.16, 0.47; p = 2.39 ⋅ 10 − 6 )]. In the meta-analysis that combined the various datasets, the association remained consistent (OR, 0.27; 95% CI, 0.17, 0.42; p = 1.34 ⋅ 10 − 8 ). In conclusion, genetic liability for higher plasma uridine levels is associated with a reduction in the risk of AF. Raising plasma uridine levels might provide new opportunities for AF prophylaxis.