| 雷梦云,杜炎宏,高耀,邓怀丽,王斌红,任智勇,刘莎.脂质体和循环代谢物与精神分裂症的关系：一项两步两样本孟德尔随机化研究[J].四川精神卫生杂志,2025,(3):223-228.Lei Mengyun,Du Yanhong,Gao Yao,Deng Huaili,Wang Binhong,Ren Zhiyong,Liu Sha,Causal relationship of liposomes and circulating metabolomes to schizophrenia： a two-step， two-sample Mendelian randomization study[J].SICHUAN MENTAL HEALTH,2025,(3):223-228 |
| 脂质体和循环代谢物与精神分裂症的关系：一项两步两样本孟德尔随机化研究 |
| Causal relationship of liposomes and circulating metabolomes to schizophrenia： a two-step， two-sample Mendelian randomization study |
| 投稿时间：2024-10-17 |
| DOI：10.11886/scjsws20241017001 |
| 中文关键词: 脂质体 循环代谢物 精神分裂症 孟德尔随机化 中介分析 |
| 英文关键词:Liposomes Circulating metabolomes Schizophrenia Mendelian randomization Mediation analysis |
| 基金项目:国家自然科学基金面上项目（项目名称：联合多模态EEG-fMRI探索磁惊厥对难治性精神分裂症额顶网络的调控机制，项目编号：82271546）；山西省留学人员科技活动择优资助项目（项目名称：rTMS辅助MST改善难治性精神分裂症认知障碍的神经机制研究，项目编号：20240041）；山西省科技创新人才团队（项目名称：重性精神障碍防治，项目编号：202304051001049）；2022年山西省回国留学人员科研资助项目（项目名称：联合多模态EEG-fMRI探索磁惊厥对难治性精神分裂症额顶网络的调控机制，项目编号：2022-190）；2024年度“六个一批”专项行动科研项目（项目名称：联合EEG-fNIRS探究MECT治疗对难治性精神分裂症疗效及其突显网络功能连接的影响，项目编号：Y2024008） |
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| 中文摘要: |
| 背景 精神分裂症是一种复杂的、严重的慢性精神障碍，其发病机制尚未完全阐明。研究表明，脂质代谢异常和循环代谢物失调在精神分裂症的发生发展中具有重要作用。然而，现有研究多局限于少数脂质体和循环代谢物，未能系统揭示循环代谢物在脂质体与精神分裂症之间的中介作用。目的 揭示循环代谢物介导的脂质体与精神分裂症之间的因果关系，以期为寻找预防和治疗精神分裂症的生物标志物和潜在治疗靶点提供参考。方法 从全基因组关联研究（GWAS）数据集中获取179种脂质体的GWAS数据集作为暴露数据，选用123种循环代谢物的GWAS数据集作为潜在的中介变量，以精神分裂症数据作为结局数据。采用逆方差加权法（IVW）、MR-Egger、中位数加权模型以及加权模型4种方法，进行两步、双样本孟德尔随机化分析，探讨脂质体与精神分裂症之间的因果关系以及循环代谢物在脂质体与精神分裂症之间的中介作用。结果 应用IVW模型确定了8种脂质体与精神分裂症相关且无反向因果关系，与精神分裂症存在因果关系的循环代谢物共5种。乙酸盐在磷脂酰肌醇（18：0_18：2）与精神分裂症之间的因果关系中起中介作用（P=0.023，95% CI：0.036~0.532），介导了28.4%的因果关系。结论 脂质体与精神分裂症存在因果关系，磷脂酰肌醇是精神分裂症发生的危险因素，乙酸盐在此过程中发挥中介作用。 |
| 英文摘要: |
| Background Schizophrenia is a complex， chronic and severe mental disorder， and the pathogenesis of which has not been fully elucidated. The abnormalities in lipid metabolism and circulating metabolomes have already been implicated in the pathophysiology of schizophrenia. However， available studies have mainly focused on a few liposomes and circulating metabolites， failing to systematically reveal the mediating role of circulating metabolomes in the causal relationship between liposomes and schizophrenia.Objective To uncover mediating role of circulating metabolomes in the causal relationship between liposomes and schizophrenia， thereby providing biomarkers and potential therapeutic targets for the prevention and treatment of schizophrenia.Methods Data from Genome-Wide Association Studies （GWAS） were analyzed， taking data on 179 liposomes as exposure variables， data on 123 circulating metabolites as intermediate variables， and data on schizophrenia as outcome variable. A two-step， two-sample Mendelian randomization analysis was conducted using the inverse-variance weighted （IVW）， MR- Egger， Weighted median， and Weighted mode methods to study the causal relationship of liposomes with schizophrenia and the mediating role of circulating metabolomes in the relationship.Results IVW model identified 8 lipids associated with schizophrenia without reverse causality. There were 5 circulating metabolomes strongly associated with schizophrenia. Acetate played a significant mediating role in the causal relationship between phosphatidylinositol （18：0_18：2） and schizophrenia （P=0.023， 95% CI： 0.036~0.532）， accounting for 28.4% of the causal relationship.Conclusion This study demonstrates a causal relationship between liposomes and schizophrenia， with phosphatidylinositol being a risk factor in the progression of schizophrenia， and acetate playing a mediating role in this process. ［Fund by National Natural Science Foundation of China General Program （number， 82271546）； Shanxi Merit Funding for Overseas Students Sci-Tech Activities Project （number， 20240041）； Shanxi Province Science and Technology Innovation Leading Talent Team Project （number， 202304051001049）； Shanxi Scientific Research Foundation for the Returned Overseas Chinese Scholars （number， 2022-190）； "Six Measures for Health Care Prosperity" Specialized Research Program （number， Y2024008）］ |
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