中国卒中杂志2025，Vol.20Issue(6)：675-685,11.DOI:10.3969/j.issn.1673-5765.2025.06.003
脂质代谢组与卒中的因果关系:系统孟德尔随机化研究
Causal Relationship between Lipid Metabolome and Stroke:A Systematic Mendelian Randomization Study
摘要
Abstract
Objective Abnormal lipid metabolism is closely associated with the occurrence and development of stroke.This study aims to explore the causal associations between lipid metabolome and stroke as well as its subtypes,and to analyze the impact of lipoprotein components on stroke. Methods Based on the GWAS of 213 lipid metabolites,as well as any stroke(AS),any ischemic stroke(AIS),and its three subtypes-large artery stroke(LAS),cardioembolic stroke(CES),and small vessel stroke(SVS),univariate Mendelian randomization(MR)methods were used to screen the lipid metabolites that have potential causal relationships with stroke.On this basis,multivariate MR methods were employed to integrate the genetic correlations among lipid metabolites,further identifying those with independent causal effects. Results In the univariate MR analysis,16,58,and 58 lipid metabolites were identified as having potential causal associations with AS,AIS,and LAS,respectively,while only one lipid metabolite was found to be associated with each of CES and SVS.There were widespread genetic correlations among these lipid metabolites.Through further screening by multivariate MR analysis,11,4,and 39 lipid metabolites with high-confidence associations with AS,AIS,and LAS were identified,respectively.Among them,small-low density lipoprotein(S-LDL),medium-low density lipoprotein(M-LDL),and the ratio of phospholipids to total lipids in small-high density lipoproteins had potential protective effects on stroke and its subtypes;while lipid components such as cholesterol and cholesterol esters in S-LDL and M-LDL were significantly associated with an increased risk of LAS. Conclusions Lipid metabolites exert the most significant effect on LAS,and the proportion of cholesterol and phospholipids in lipoprotein particles plays differentiated roles in the occurrence and development of stroke.关键词
脂质代谢组/卒中/孟德尔随机化/因果关联Key words
Lipid metabolome/Stroke/Mendelian randomization/Causal association分类
医药卫生引用本文复制引用
姜明慧,许喆,石延枫,张杰,李昊,程丝..脂质代谢组与卒中的因果关系:系统孟德尔随机化研究[J].中国卒中杂志,2025,20(6):675-685,11.基金项目
国家重点研发计划(2022YFE0209600)国家自然科学基金(82471304)中国科协青年人才托举工程(2023QNRC001) （2022YFE0209600）
