He Menghao, Xu Chun, Yang Renyi, Liu Lijuan, Zhou Desheng, Yan Siyang
The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China.
Hunan University of Chinese Medicine, Changsha, Hunan, China.
Front Genet. 2024 Jan 19;15:1333454. doi: 10.3389/fgene.2024.1333454. eCollection 2024.
Ischemic stroke (IS) is a major cause of death and disability worldwide. Previous studies have reported associations between metabolic disorders and IS. However, evidence regarding the causal relationship between blood metabolites and IS lacking. A two-sample Mendelian randomization analysis (MR) was used to assess the causal relationship between 1,400 serum metabolites and IS. The inverse variance-weighted (IVW) method was employed to estimate the causal effect between exposure and outcome. Additionally, MR-Egger regression, weighted median, simple mode, and weighted mode approaches were employed as supplementary comprehensive evaluations of the causal effects between blood metabolites and IS. Tests for pleiotropy and heterogeneity were conducted. After rigorous selection, 23 known and 5 unknown metabolites were identified to be associated with IS. Among the 23 known metabolites, 13 showed significant causal effects with IS based on 2 MR methods, including 5-acetylamino-6-formylamino-3-methyluracil, 1-ribosyl-imidazoleacetate, Behenoylcarnitine (C22), N-acetyltyrosine, and N-acetylputrescine to (N (1) + N (8))-acetate,these five metabolites were positively associated with increased IS risk. Xanthurenate, Glycosyl-N-tricosanoyl-sphingadienine, Orotate, Bilirubin (E,E), Bilirubin degradation product, CHNO, Bilirubin (Z,Z) to androsterone glucuronide, Bilirubin (Z,Z) to etiocholanolone glucuronide, Biliverdin, and Uridine to pseudouridine ratio were associated with decreased IS risk. Among 1,400 blood metabolites, this study identified 23 known metabolites that are significantly associated with IS risk, with 13 being more prominent. The integration of genomics and metabolomics provides important insights for the screening and prevention of IS.
缺血性中风（IS）是全球范围内死亡和残疾的主要原因。先前的研究报道了代谢紊乱与IS之间的关联。然而，关于血液代谢物与IS之间因果关系的证据尚缺乏。本研究采用两样本孟德尔随机化分析（MR）来评估1400种血清代谢物与IS之间的因果关系。采用逆方差加权（IVW）方法估计暴露与结局之间的因果效应。此外，采用MR-Egger回归、加权中位数、简单模式和加权模式方法作为对血液代谢物与IS之间因果效应的补充综合评估。进行了多效性和异质性检验。经过严格筛选，确定了23种已知代谢物和5种未知代谢物与IS相关。在这23种已知代谢物中，基于两种MR方法，有13种与IS存在显著因果效应，包括5-乙酰氨基-6-甲酰氨基-3-甲基尿嘧啶、1-核糖基-咪唑乙酸、山嵛酰肉碱（C22）、N-乙酰酪氨酸和N-乙酰腐胺至（N（1）+N（8））-乙酸盐，这五种代谢物与IS风险增加呈正相关。黄尿酸、糖基-N-二十三烷酰-鞘氨二烯、乳清酸、胆红素（E，E）、胆红素降解产物、CHNO、胆红素（Z，Z）至雄酮葡糖苷酸、胆红素（Z，Z）至本胆烷醇酮葡糖苷酸、胆绿素和尿苷至假尿苷比值与IS风险降低相关。在1400种血液代谢物中，本研究确定了23种与IS风险显著相关的已知代谢物，其中13种更为突出。基因组学和代谢组学的整合为IS的筛查和预防提供了重要见解。
