Wang Yaolou, Shen Yingjie, Li Qi, Xu Hangjia, Gao Aili, Li Kuo, Rong Yiwei, Gao Shang, Liang Hongsheng, Zhang Xiangtong
Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
School of Life Science, Northeast Agricultural University, Harbin, Heilongjiang, China.
Front Nutr. 2024 May 15;11:1376889. doi: 10.3389/fnut.2024.1376889. eCollection 2024.
Hemorrhagic stroke (HS), a leading cause of death and disability worldwide, has not been clarified in terms of the underlying biomolecular mechanisms of its development. Circulating metabolites have been closely associated with HS in recent years. Therefore, we explored the causal association between circulating metabolomes and HS using Mendelian randomization (MR) analysis and identified the molecular mechanisms of effects.
We assessed the causal relationship between circulating serum metabolites (CSMs) and HS using a bidirectional two-sample MR method supplemented with five ways: weighted median, MR Egger, simple mode, weighted mode, and MR-PRESSO. The Cochran Q-test, MR-Egger intercept test, and MR-PRESSO served for the sensitivity analyses. The Steiger test and reverse MR were used to estimate reverse causality. Metabolic pathway analyses were performed using MetaboAnalyst 5.0, and genetic effects were assessed by linkage disequilibrium score regression. Significant metabolites were further synthesized using meta-analysis, and we used multivariate MR to correct for common confounders.
We finally recognized four metabolites, biliverdin (OR 0.62, 95% CI 0.40-0.96, = 0.030), linoleate (18. 2n6) (OR 0.20, 95% CI 0.08-0.54, = 0.001),1-eicosadienoylglycerophosphocholine* (OR 2.21, 95% CI 1.02-4.76, = 0.044),7-alpha-hydroxy-3 -oxo-4-cholestenoate (7-Hoca) (OR 0.27, 95% CI 0.09-0.77, = 0.015) with significant causal relation to HS.
We demonstrated significant causal associations between circulating serum metabolites and hemorrhagic stroke. Monitoring, diagnosis, and treatment of hemorrhagic stroke by serum metabolites might be a valuable approach.
出血性中风（HS）是全球范围内导致死亡和残疾的主要原因，但其发病的潜在生物分子机制尚未明确。近年来，循环代谢物与HS密切相关。因此，我们使用孟德尔随机化（MR）分析探讨了循环代谢组与HS之间的因果关系，并确定了其作用的分子机制。
我们使用双向双样本MR方法，并辅以加权中位数、MR-Egger、简单模式、加权模式和MR-PRESSO这五种方法，评估循环血清代谢物（CSM）与HS之间的因果关系。采用Cochran Q检验、MR-Egger截距检验和MR-PRESSO进行敏感性分析。使用Steiger检验和反向MR来估计反向因果关系。使用MetaboAnalyst 5.0进行代谢途径分析，并通过连锁不平衡评分回归评估基因效应。使用荟萃分析进一步综合显著代谢物，并使用多变量MR校正常见混杂因素。
我们最终识别出四种与HS有显著因果关系的代谢物，即胆红素（比值比0.62，95%置信区间0.40 - 0.96，P = 0.030）、亚油酸（18:2n6）（比值比0.20，95%置信区间0.08 - 0.54，P = 0.001）、1-二十碳二烯酰甘油磷酸胆碱*（比值比2.21，95%置信区间1.02 - 4.76，P = 0.044）、7-α-羟基-3-氧代-4-胆甾烯酸（7-Hoca）（比值比0.27，95%置信区间0.09 - 0.77，P = 0.015）。
我们证明了循环血清代谢物与出血性中风之间存在显著的因果关系。通过血清代谢物对出血性中风进行监测、诊断和治疗可能是一种有价值的方法。
