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| 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 |
| The Causal Association between Liposomes and Circulating Metabolites and Schizophrenia: A Two-Step, Two-Sample Mendelian Randomization Study |
| 投稿时间：2024-10-17 修订日期：2025-04-22 |
| DOI： |
| 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:Lipids Circulating metabolites Schizophrenia Mendelian randomization Mediation analysis |
| 基金项目:国家自然科学基金面上项目（82271546）；山西省留学人员科技活动择优资助项目（20240041）；山西省科技创新人才团队（202304051001049）；2022年山西省筹资金资助回国留学人员科研项目（2022-190）；2024年度“六个一批”专项行动科研项目（Y2024008） |
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| 中文摘要: |
| 背景：精神分裂症（SZ）是一种复杂的慢性重型精神障碍，其发病机制复杂且未完全阐明，但研究表明脑脂质失调、脂质代谢异常、氧化应激和炎症反应等在SZ的病理生理学中扮演关键角色，且与认知功能密切相关。
目的：本研究旨在使用双样本孟德尔随机化来研究循环代谢物介导脂质体与SZ之间的因果关系。
方法：本研究从全基因组关联研究（genome? wide association study，GWAS）目录库中获取了178种脂质体的GWAS数据集作为研究的暴露数据，选用123种循环代谢物的GWAS数据集作为潜在的中介变量， SZ数据作为结局的数据。采用逆方差加权法（inverse variance weighted, IVW）等4种方法进行了两步、双样本孟德尔随机化分析，以研究脂质对SZ的因果关系以及循环代谢物在脂质体和SZ之间的介导作用，同时进行了异质性检验来确保结果的稳健性。
结果：应用IVW模型确定了8种脂质体与SZ相关，且无反向因果关系。与SZ具有强相关性的循环代谢物共有5种，磷脂酰肌醇（18:0_18:2）与SZ存在显著的正相关因果关系 [OR =1.059，95% CI= 1.022~1.098]，且乙酸盐在磷脂酰肌醇（18:0_18:2）与SZ之间起到了显著的中介作用（IE= 0.014，DE= 0.035，TE= 0.049，中介效应占比= 0.284，P= 0.023，中介效应占比CI= 0.036~0.532）。
结论：本研究表明，脂质体和SZ之间存在因果关系，磷脂酰肌醇是SZ进展当中的危险因素，并且在此过程中乙酸盐起着介导作用。 |
| 英文摘要: |
| Background Schizophrenia (SZ) is a complex chronic severe mental disorder with a complex and not fully elucidated pathogenesis, but studies indicate that brain lipid dysregulation, lipid metabolism abnormalities, oxidative stress, and inflammatory responses play key roles in the pathophysiology of SZ and are closely related to cognitive function.
Objective The purpose of this study is to investigate the causal relationship between circulating metabolites mediating lipids and schizophrenia (SZ) using two-sample Mendelian randomization and mediation analysis. Methods This study obtained genome? wide association study (GWAS) datasets for 178 lipids from the GWAS Catalog as exposure data, selected GWAS datasets for 123 circulating metabolites as potential mediators, and used SZ data as outcome data. The main approach was two-step, two-sample Mendelian randomization analysis using the inverse variance weighted (IVW) and three other methods to study the causal relationship of lipids with SZ and the mediating role of circulating metabolites between lipids and SZ. Heterogeneity tests were also conducted to ensure the robustness of the results. Results The application of the IVW model identified 8 lipids associated with SZ without reverse causality. There were 5 circulating metabolites strongly associated with SZ, notably phosphatidylinositol (18:0_18:2), which showed a significant positive causal relationship with SZ [OR = 1.059, 95% CI = 1.022~1.098]. Acetate played a significant mediating role between phosphatidylinositol (18:0_18:2) and SZ (IE = 0.014, DE = 0.035, TE = 0.049, proportion of mediation effect = 0.284, P = 0.023, confidence interval for the proportion of mediation effect = 0.036~0.532). Conclusion This study demonstrates a causal relationship between lipids and SZ, with phosphatidylinositol being a risk factor in the progression of SZ, and acetate playing a mediating role in this process. |
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