利用两样本孟德尔随机化研究人类血液代谢物与冠状动脉疾病之间的因果关系
[Investigating the causal relationship between human blood metabolites and coronary artery disease using two-sample Mendelian randomization].
作者信息
Wang Z, Lai W, Zhong S
机构信息
School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China.
Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
出版信息
Nan Fang Yi Ke Da Xue Xue Bao. 2021 Feb 25;41(2):272-278. doi: 10.12122/j.issn.1673-4254.2021.02.16.
OBJECTIVE
To explore the causal relationship between blood metabolites and the risk of coronary artery disease (CAD) using a two-sample Mendelian randomization (MR) approach.
OBJECTIVE
Based on the data from a large-scale metabolome-based genome-wide association study (mGWAS) and the GWAS of CAD, we investigated the causality between blood metabolites and CAD using an inverse variance weighted (IVW) method and another 4 two-sample MR models. Heterogeneity, horizontal pleiotropy, and sensitivity tests were performed to evaluate the stability and reliability of the results.
OBJECTIVE
Among the 486 blood metabolites, 32 metabolites showed nominally causative association with CAD with the IVW method ( < 0.05), including 11 known metabolites and 21 unknown metabolites. Three known metabolites [N-acetylornithine, bradykinin-des-arg(9), and succinylcarnitine] were statistically significant in at least 3 MR models, but their causal effects on CAD were no longer significant after sensitivity analysis using leave-one-out method and elimination of the confounding instrumental variables.
OBJECTIVE
There is no strong evidence to support a robust causal relationship between the 486 blood metabolites and the risk of CAD.
目的
采用两样本孟德尔随机化（MR）方法探讨血液代谢物与冠状动脉疾病（CAD）风险之间的因果关系。
目的
基于大规模代谢组全基因组关联研究（mGWAS）和CAD的全基因组关联研究（GWAS）数据，我们使用逆方差加权（IVW）方法和另外4种两样本MR模型研究了血液代谢物与CAD之间的因果关系。进行了异质性、水平多效性和敏感性检验以评估结果的稳定性和可靠性。
目的
在486种血液代谢物中，32种代谢物通过IVW方法显示出与CAD名义上的因果关联（<0.05），包括11种已知代谢物和21种未知代谢物。三种已知代谢物[N-乙酰鸟氨酸、缓激肽-去-精氨酸（9）和琥珀酰肉碱]在至少3种MR模型中具有统计学意义，但在使用留一法进行敏感性分析并消除混杂的工具变量后，它们对CAD的因果效应不再显著。
目的
没有强有力的证据支持486种血液代谢物与CAD风险之间存在稳健的因果关系。
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