The causal effects of genetically determined human blood metabolites on the risk of atrial fibrillation

Abstract

BackgroundBlood metabolites have been found related to atrial fibrillation (AF), but the causal role is still unclear. Mendel randomization (MR) can give information about the causality between blood metabolites and AF.MethodsTwo-sample MR analysis was used to evaluate the causality between 486 blood metabolites and AF. Firstly, the genome-wide association study (GWAS) data for AF (from Nielsen et al.) was analyzed and some metabolites were identified. Then another GWAS data for AF (from Roselli et al.) was repeatedly analyzed to verify the results. Inverse variance weighted method was mainly used to determine the causality, and MR-egger, Weighted Median, and MR-PRESSO models were used as supplements of MR. Cochran's Q test was used to assess heterogeneity. And MR-Egger intercept and MR-PRESSO global test were performed to measure pleiotropy.ResultsThe study used Bonferroni's corrected P value (P < 1.03 × 10−4) as the significance threshold. After MR analysis and replication analysis, we found two overlapped metabolites. Among which tryptophan betaine was the most significant causal metabolite in both AF GWAS data (from Nielsen et al.) (odds ratio (OR) = 0.83, 95% confidence interval (CI) = 0.76–0.90, P = 9.37 × 10−6) and AF GWAS data (from Roselli et al.) (OR = 0.82, 95% CI = 0.76–0.88, P = 2.00 × 10−7), while uridine was nominally significant metabolites in both AF GWAS data (from Nielsen et al.) (OR = 0.58, 95% CI = 0.40–0.84, P = 0.004) and AF GWAS data (from Roselli et al.) (OR = 0.56, 95% CI = 0.35–0.88, P = 0.01). And the results of sensitivity analysis showed that none of them had obvious heterogeneity or pleiotropy.ConclusionThe study identified several blood metabolites that were causally related to AF, which may provide new perspectives on the pathogenesis of AF.

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

“…A recent MR investigation proposed similar conclusions with us. Their independent study extracted different IVs with a significant threshold at p < 1 × 10 -5 and came to similar results 44 .…”

Protective Effect of Uridine on Structural and Functional Rearrangements in Heart Mitochondria after a High-Dose Isoprenaline Exposure Modelling Stress-Induced Cardiomyopathy in Rats

“…Uridine is involved in cellular signaling through P2Y receptors and can modulate systemic metabolism [47]. Recent data revealed that a higher level of plasma uridine reduces the tendency for atrial fibrillation and can be associated with a decreased atherosclerosis risk [48,49]. Our previous studies indicated that under ischemia and reperfusion conditions, uridine supplementation prevents myocardial redox dyshomeostasis and heart rhythm disorders [29,30].…”