血清脂质组与胶质母细胞瘤因果关联的孟德尔随机化研究  

A mendelian randomized study of the causal association between serum lipidome and glioblastoma

作　　者：孙瑛玮 王格宇 戴雪健 杨若宇 宁一晟 冯思哲 Sun Yingwei;Wang Geyu;Dai Xuejian;Yang Ruoyu;Ning Yisheng;Feng Sizhe(Graduate Training Base of General Hospital of Northern Theater Command,Dalian Medical University,Shenyang,Liaoning 110016,China;Graduate Training Base of General Hospital of Northern Theater Command,China Medical University,Shenyang,Liaoning 110016,China;Department of Neurosurgery,General Hospital of Northern Theater Command,Shenyang,Liaoning 110016,China)

机构地区：[1]大连医科大学北部战区总医院研究生培养基地,辽宁沈阳110016 [2]中国医科大学北部战区总医院研究生培养基地,辽宁沈阳110016 [3]北部战区总医院神经外科,辽宁沈阳110016

出　　处：《中国微侵袭神经外科杂志》2025年第1期52-58,共7页Chinese Journal of Minimally Invasive Neurosurgery

基　　金：辽宁省民生科技计划项目(编号:2021JH2/10300116)。

摘　　要：目的 利用两样本双向孟德尔随机化方法探究血清脂质组与胶质母细胞瘤(glioblastoma,GBM)之间潜在的因果关系。方法 使用公开的血清脂质组与GBM的全基因组关联研究(genome-wide association study,GWAS)统计数据,将与脂质性状有关的单核苷酸多态性(single nucleotide Polymorphisms,SNP)作为工具变量(instrumental variables,IV),因果效应评估采用逆方差加权法(inverse-variance weighted,IVW),结合贝叶斯加权孟德尔随机化(Bayesian weighted Mendelian randomization,BWMR)进行因果关系的补充验证。使用留一法、异质性检验、水平基因多效性检验来验证结果稳定性和可靠性。结果 MR分析结合BWMR分析,且经FDR校正后,11种血清脂质与GBM风险相关(P<0.05),其中磷脂酰乙醇胺(18:0_0:0)、磷脂酰胆碱(16:0_18:2)、磷脂酰胆碱(16:0_20:2)、磷脂酰胆碱(18:1_18:1)、磷脂酰胆碱(18:1_18:2)、磷脂酰胆碱(18:1_20:2)、磷脂酰胆碱(18:2_18:2)、磷脂酰胆碱(O-16:0_18:1)为GBM发病危险因素;磷脂酰肌醇(18:0_20:4)、鞘磷脂(d38:2)、三酰甘油(56:6)为GBM发病保护因素。敏感性分析未发现存在显著异质性和水平多效性。结论 特定血清脂质对GBM发病风险具有一定因果关联。Objective To investigate the potential causal relationship between serum lipidome and glioblastoma(GBM)using a two-sample bidirectional Mendelian randomization(MR).Methods This study utilized publicly available genome-wide association study(GWAS)summary statistics for serum lipidome and GBM.Single nucleotide polymorphisms(SNPs)associated with serum lipidome were employed as instrumental variables(IV).The causal effects were primarily assessed using the inverse-variance weighted(IVW)method,supplemented by Bayesian weighted Mendelian randomization(BWMR)to further elucidate the causal relationships.Sensitivity analyses,including leave-one-out analysis,heterogeneity tests,and horizontal pleiotropy assessments,were conducted to evaluate the stability and reliability of the results.Results After MR analysis combined with BWMR analysis and correction for false discovery rate(FDR),11 serum lipids were found to be associated with GBM risk(P<0.05).Specifically,phosphatidylethanolamine(18:0_0:0),phosphatidylcholine(16:0_18:2),phosphatidylcholine(16:0_20:2),phosphatidylcholine(18:1_18:1),phosphatidylcholine(18:1_18:2),phosphatidylcholine(18:1_20:2),phosphatidylcholine(18:2_18:2),and phosphatidylcholine(O-16:0_18:1)were identified as risk factors for GBM.Conversely,phosphatidylinositol(18:0_20:4),sphingomyelin(d38:2),and triacylglycerol(56:6)as protective factors against GBM.Sensitivity analyses did not reveal significant heterogeneity or horizontal pleiotropy.Conclusions Specific serum lipids may have a causal association with the risk of GBM.

关 键 词：胶质母细胞瘤 脂质组学 多态性 单核苷酸 孟德尔随机化分析 

分 类 号：R739.41[医药卫生—肿瘤] R730.2[医药卫生—临床医学]