Yu Zhao, Shen Yingjie, Zhang Haopeng, Zhang Wei, Zhang Xi, Wang Yaolou, Nie Chenyi, Zhou Jiaxin, Gao Aili, Liang Hongsheng
NHC Key Laboratory of Cell Transplantation, Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
School of Life Science, Northeast Agricultural University, Harbin, Heilongjiang, China.
J Stroke Cerebrovasc Dis. 2025 Apr;34(4):108252. doi: 10.1016/j.jstrokecerebrovasdis.2025.108252. Epub 2025 Jan 26.
Recent research indicates that the plasma lipidome composition may undergo alterations following hemorrhagic stroke. Nevertheless, the causal inference between plasma lipidome and hemorrhagic stroke remains elusive.
Exposure data were achieved from a recent Genome-wide Association Study (GWAS) study of 179 lipid species involving 7174 individuals, while the outcome data were obtained from the FinnGen consortium (R10), including intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and non-traumatic intracranial hemorrhage (nITH). Two-sample bidirectional Mendelian randomization (MR) analyses were used to assess the causal inference between lipidome and hemorrhagic stroke, and inverse variance weighted served as the main method. Genetic correlations between lipidome and hemorrhagic stroke were assessed using linkage disequilibrium score regression (LDSC).
After the false discovery rate (FDR) correction, Phosphatidylcholine (O-18:2_20:4) was identified as a substantial risk factor for ICH (OR,1.199; 95 % CI, 1.073-1.341; P = 0.073). Alternatively, Phosphatidylinositol (16:0_18:1) was a relevant protective factor (OR, 0.773; 95 % CI, 0.666-0.896; P = 0.069). Furthermore, the Sterol ester (27:1/20:3) (OR, 1.138; 95 % CI, 1.024-1.264; P = 0.086) was identified as the prominent risk factor for SAH. Finally, Sterol ester (27:1/20:4) (OR, 1.073; 95 % CI, 1.026-1.121; P = 0.030) and Phosphatidylinositol (16:0_18:1) levels (OR, 0.794; 95 % CI, 0.709-0.889; P = 0.007) was identified as risk and protective factors for nITH, respectively.
The causal relationship between plasma lipidome and hemorrhagic stroke is evident. Studying the plasma lipidome offers promising preventive strategies and potential therapeutic approaches for hemorrhagic stroke.
近期研究表明，出血性中风后血浆脂质组组成可能会发生改变。然而，血浆脂质组与出血性中风之间的因果推断仍不明确。
暴露数据来自一项近期针对7174名个体的179种脂质的全基因组关联研究（GWAS），而结局数据来自芬兰基因联盟（R10），包括脑出血（ICH）、蛛网膜下腔出血（SAH）和非创伤性颅内出血（nITH）。采用两样本双向孟德尔随机化（MR）分析来评估脂质组与出血性中风之间的因果推断，逆方差加权法作为主要方法。使用连锁不平衡评分回归（LDSC）评估脂质组与出血性中风之间的遗传相关性。
在错误发现率（FDR）校正后，磷脂酰胆碱（O - 18:2_20:4）被确定为脑出血的一个重要危险因素（比值比，1.199；95%置信区间，1.073 - 1.341；P = 0.073）。另外，磷脂酰肌醇（16:0_18:1）是一个相关的保护因素（比值比，0.773；95%置信区间，0.666 - 0.896；P = 0.069）。此外，甾醇酯（27:1/20:3）（比值比，1.138；95%置信区间，1.024 - 1.264；P = 0.086）被确定为蛛网膜下腔出血的主要危险因素。最后，甾醇酯（27:1/20:4）（比值比，1.073；95%置信区间，1.026 - 1.121；P = 0.030）和磷脂酰肌醇（16:0_18:1）水平（比值比，0.794；95%置信区间，0.709 - 0.889；P = 0.007）分别被确定为非创伤性颅内出血的危险因素和保护因素。
血浆脂质组与出血性中风之间的因果关系是明显的。研究血浆脂质组为出血性中风提供了有前景的预防策略和潜在的治疗方法。
