Cheng Tao, Wang Huan, Hu Yuanhui
Department of Cardiological Medicine, China Academy of Chinese Medical Sciences Guang'anmen Hospital, Beijing, China.
Beijing University of Chinese Medicine, Beijing, China.
Front Cardiovasc Med. 2023 Jul 26;10:1211458. doi: 10.3389/fcvm.2023.1211458. eCollection 2023.
Blood 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.
Two-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 test was used to assess heterogeneity. And MR-Egger intercept and MR-PRESSO global test were performed to measure pleiotropy.
The study used Bonferroni's corrected value ( < 1.03 × 10) 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, = 9.37 × 10) and AF GWAS data (from Roselli et al.) (OR = 0.82, 95% CI = 0.76-0.88, = 2.00 × 10), while uridine was nominally significant metabolites in both AF GWAS data (from Nielsen et al.) (OR = 0.58, 95% CI = 0.40-0.84, = 0.004) and AF GWAS data (from Roselli et al.) (OR = 0.56, 95% CI = 0.35-0.88, = 0.01). And the results of sensitivity analysis showed that none of them had obvious heterogeneity or pleiotropy.
The study identified several blood metabolites that were causally related to AF, which may provide new perspectives on the pathogenesis of AF.
血液代谢物已被发现与心房颤动（AF）有关，但因果关系仍不明确。孟德尔随机化（MR）可以提供有关血液代谢物与AF之间因果关系的信息。
采用两样本MR分析来评估486种血液代谢物与AF之间的因果关系。首先，分析了AF的全基因组关联研究（GWAS）数据（来自尼尔森等人），并确定了一些代谢物。然后，对另一组AF的GWAS数据（来自罗塞利等人）进行重复分析以验证结果。主要使用逆方差加权法来确定因果关系，MR-egger、加权中位数和MR-PRESSO模型用作MR的补充。采用 Cochr an检验评估异质性。并进行MR-Egger截距和MR-PRESSO全局检验以测量多效性。
该研究使用Bonferroni校正的 值（<1.03×10）作为显著性阈值。经过MR分析和重复分析，我们发现了两种重叠的代谢物。其中，在AF的GWAS数据（来自尼尔森等人）（比值比（OR）=0.83，95%置信区间（CI）=0.76-0.90，=9.37×10）和AF的GWAS数据（来自罗塞利等人）（OR=0.82，95%CI=0.76-0.88，=2.00×10）中，色氨酸甜菜碱都是最显著的因果代谢物，而尿苷在AF的GWAS数据（来自尼尔森等人）（OR=0.58，95%CI=0.40-0.84，=0.004）和AF的GWAS数据（来自罗塞利等人）（OR=0.56，95%CI=0.35-0.88，=0.01）中都是名义上显著的代谢物。敏感性分析结果表明，它们均无明显的异质性或多效性。
该研究确定了几种与AF存在因果关系的血液代谢物，这可能为AF的发病机制提供新的视角。
