Ye Qian, Zhou Yilin, Xu Kai, Jiang Zhili
Department of Clinical Laboratory, Wenzhou People's Hospital, The Third Affiliated Hospital of Shanghai University, The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang, China.
College of Engineering, Boston University, Boston, MA, United States.
Front Nutr. 2024 Sep 3;11:1421531. doi: 10.3389/fnut.2024.1421531. eCollection 2024.
Peripheral arteriosclerosis is caused by any atherosclerosis outside the heart and brain. However, the underlying biological mechanisms are not fully understood. This study aims to explore the causal relationship between blood metabolites and peripheral arteriosclerosis.
A Mendelian randomization (MR) analysis was implemented to estimate the causality of blood metabolites on peripheral arteriosclerosis. A genome-wide association study (GWAS) of 1,400 metabolites was used as the exposure, whereas two different GWAS datasets of peripheral arteriosclerosis were the outcomes. Inverse-variance weighted (IVW) was the main analysis of causal analysis. MR-Egger, the simple mode, weighted median and weighted mode were used to increase the stability and robustness of the results. Cochran Q test, MR-Egger intercept test, the funnel plot, and MR-Pleiotropy RESidual Sum and Outlier were used for sensitivity analyses. Furthermore, metabolic pathway enrichment analysis was performed using MetaboAnalyst5.0.
In this MR study, eight blood metabolites have a strong causal relationship with peripheral arteriosclerosis, including 1-myristoyl-2-arachidonoyl-GPC (14:0/20:4), 1-palmitoyl-2-arachidonoyl-gpc (16:0/20:4n6), 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE, 1-palmitoyl-2-dihomo-linolenoyl-GPC, Gamma-glutamylleucine, Deoxycholic acid glucuronide and two named X- (X-24546, X-26111). In addition, five important metabolic pathways in peripheral arteriosclerosis were identified through metabolic pathway analysis.
This study provides evidence for the causal relationship between blood metabolites and peripheral arteriosclerosis, and these eight blood metabolites provide new perspectives for screening and prevention of peripheral arteriosclerosis in the future.
外周动脉硬化是由心脏和大脑以外的任何动脉粥样硬化引起的。然而,其潜在的生物学机制尚未完全明确。本研究旨在探讨血液代谢物与外周动脉硬化之间的因果关系。
采用孟德尔随机化(MR)分析来评估血液代谢物对外周动脉硬化的因果关系。以1400种代谢物的全基因组关联研究(GWAS)作为暴露因素,而外周动脉硬化的两个不同GWAS数据集作为结果。逆方差加权(IVW)是因果分析的主要方法。采用MR-Egger、简单模式、加权中位数和加权模式来提高结果的稳定性和稳健性。使用Cochran Q检验、MR-Egger截距检验、漏斗图和MR-多效性残差和离群值进行敏感性分析。此外,使用MetaboAnalyst5.0进行代谢途径富集分析。
在这项MR研究中,八种血液代谢物与外周动脉硬化有很强的因果关系,包括1-肉豆蔻酰-2-花生四烯酰-GPC(14:0/20:4)、1-棕榈酰-2-花生四烯酰-gpc(16:0/20:4n6)、1-(1-烯基-硬脂酰)-2-花生四烯酰-GPE、1-棕榈酰-2-二高-γ-亚麻酰-GPC、γ-谷氨酰亮氨酸、脱氧胆酸葡萄糖醛酸和两种命名为X的物质(X-24546、X-26111)。此外,通过代谢途径分析确定了外周动脉硬化中的五条重要代谢途径。
本研究为血液代谢物与外周动脉硬化之间的因果关系提供了证据,这八种血液代谢物为未来外周动脉硬化的筛查和预防提供了新的视角。