Zhang Xingkai, Zhu Xiaoyu, Shi Qinghai
Department of Graduate School, Xinjiang Medical University, Urumqi, China.
Department of Clinical Laboratory Diagnostic Center, General Hospital of Xinjiang Military Command, Urumqi, China.
Front Neurol. 2024 Jul 30;15:1432878. doi: 10.3389/fneur.2024.1432878. eCollection 2024.
Hemorrhagic stroke, characterized by acute bleeding due to cerebrovascular lesions, is associated with plasma lipids and endothelial damage. The causal relationship between genetic plasma lipid levels and hemorrhagic stroke remains unclear. This study employs a two-sample Mendelian randomization (MR) analysis to explore the causal relationship between plasma lipid profiles with different fatty acid chains and the risk of intracerebral and subarachnoid hemorrhage, the two main subtypes of hemorrhagic stroke.
The datasets for exposure and outcome summary statistics were obtained from publicly available sources such as the GWAS Catalog, IEU OpenGWAS project, and FinnGen. The two-sample MR analysis was employed to initially assess the causal relationship between 179 plasma lipid species and the risk of intracerebral and subarachnoid hemorrhage in the Finnish population, leading to the identification of candidate lipids. The same methods were applied to reanalyze data from European populations and conduct a meta-analysis of the candidate lipids. The Inverse Variance Weighting (IVW) method served as the primary analysis for causal inference, with additional methods used for complementary analyses. Sensitivity analysis was conducted to clarify causal relationships and reduce biases.
Two analyses using Mendelian randomization were performed, followed by meta-analyses of the results. A causal relationship was established between 11 specific lipid species and the occurrence of intracerebral hemorrhage within the European population. Additionally, 5 distinct lipid species were associated with subarachnoid hemorrhage. Predominantly, lipids with linoleic acid and arachidonic acid side chains were identified. Notably, lipids containing arachidonic acid chains (C20:4) such as PC 18:1;0_20:4;0 consistently showed a decreased risk of both intracerebral hemorrhage [ < 0.001; OR(95% CI) = 0.892(0.835-0.954)] and subarachnoid hemorrhage [ = 0.002; OR(95% CI) = 0.794(0.689-0.916)]. Conversely, lipids with linoleic acid chains (C18:2) were associated with an increased risk of intracerebral hemorrhage.
This study identifies a potential causal relationship between lipids with different fatty acid side chains and the risk of intracerebral and subarachnoid hemorrhagic stroke, improving the understanding of the mechanisms behind the onset and progression of hemorrhagic stroke.
出血性卒中以脑血管病变导致的急性出血为特征，与血脂和内皮损伤有关。血浆脂质水平的遗传因素与出血性卒中之间的因果关系尚不清楚。本研究采用两样本孟德尔随机化（MR）分析，以探讨具有不同脂肪酸链的血脂谱与出血性卒中的两种主要亚型——脑出血和蛛网膜下腔出血风险之间的因果关系。
暴露和结局汇总统计数据集来自公开可用的来源，如全基因组关联研究（GWAS）目录、IEU OpenGWAS项目和芬兰基因研究（FinnGen）。采用两样本MR分析初步评估179种血脂种类与芬兰人群脑出血和蛛网膜下腔出血风险之间的因果关系，从而确定候选脂质。应用相同方法重新分析欧洲人群的数据，并对候选脂质进行荟萃分析。逆方差加权（IVW）方法作为因果推断的主要分析方法，其他方法用于补充分析。进行敏感性分析以阐明因果关系并减少偏差。
进行了两项孟德尔随机化分析，随后对结果进行了荟萃分析。在欧洲人群中，确定了11种特定脂质种类与脑出血的发生之间存在因果关系。此外，5种不同的脂质种类与蛛网膜下腔出血有关。主要鉴定出含有亚油酸和花生四烯酸侧链的脂质。值得注意的是，含有花生四烯酸链（C20:4）的脂质，如PC 18:1;0_20:4;0，始终显示出脑出血[<0.001；比值比（95%置信区间）=0.892（0.835 - 0.954）]和蛛网膜下腔出血[=0.002；比值比（95%置信区间）=0.794（0.689 - 0.916）]风险降低。相反，含有亚油酸链（C18:2）的脂质与脑出血风险增加有关。
本研究确定了具有不同脂肪酸侧链的脂质与脑出血和蛛网膜下腔出血性卒中风险之间的潜在因果关系，增进了对出血性卒中发病和进展背后机制的理解。
