血浆脂质组对神经精神疾病的相互作用:一项双向孟德尔随机研究。

IF 4.3 2区 医学 Q1 NEUROSCIENCES
Molecular Neurobiology Pub Date : 2025-10-01 Epub Date: 2025-06-03 DOI:10.1007/s12035-025-05105-y
Xiao Xiao, Xiaolei Luo, Yanyun Wang, Xinmin Pan, Linbo Gao, Shanling Liu, Lin Zhang
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引用次数: 0

摘要

脂质代谢紊乱与神经和精神障碍有关;血浆脂质组学作为诊断和治疗靶点具有广阔的前景。然而,血浆脂质与神经精神疾病(npd)之间的因果关系尚不清楚。我们采用双向孟德尔随机化(MR)来检验179种血浆脂质与17种npd之间的因果关系。通过链接不平衡评分回归(LDSC)、贝叶斯共定位(COLOC)分析和中介分析,进一步研究了正向MR中的显著关联。正向磁共振显示,甾醇酯(27:1/16:1)和二酰基甘油(16:0 ~ 18:2)升高可能增加神经性厌食症(AN)的风险,而鞘磷脂(d36:2)升高可能降低其风险。LDSC分析显示三种脂质与AN之间没有实质性的遗传联系,而COLOC测试的低后验概率假设4质疑了共享变体的存在。此外,甾醇酯(27:1/16:1)升高的AN风险可能通过C-X-C趋化因子10下调介导。在反向MR中,我们发现了多种因果关系:ADHD增加了固醇酯(27:1/20:3),磷脂酰胆碱(18:0_20:3,18:1_20:3);阿尔茨海默病降低磷脂酰胆碱(0 - 18:1:20:3);缺血性中风与低磷脂酰胆碱相关(16:0_0:0);强迫症表现出磷脂酰胆碱(16:1_18 . 0)上调和甾醇酯(27:1 . 22:6)下调的双重效应;帕金森病与二酰基甘油较少有关(18:1_18:3);精神分裂症与更多的甘油三酯有关(48:0,51:1);偏头痛降低甾醇酯(27:1/20:2)。这些见解揭示了血浆脂质与神经精神疾病之间的因果关系。我们的研究结果扩展了血浆脂质组与npd之间的因果关系,为发现这些疾病的新生物标志物和治疗靶点提供了见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Interactive Effect of Plasma Lipidome on Neuropsychiatric Disorders: A Bidirectional Mendelian Randomization Study.

Lipid metabolism disruptions are implicated in nervous and mental disorders; plasma lipidomics show promise as diagnostic and therapeutic targets. However, clarification of causal relationships between plasma lipids and neuropsychiatric disorders (NPDs) remains unclear. We employed bidirectional Mendelian randomization (MR) to examine causal links between 179 plasma lipids and 17 NPDs. Significant associations in the forward MR were further investigated using linkage disequilibrium score regression (LDSC), Bayesian colocalization (COLOC) analysis, and mediation analysis. Forward MR revealed sterol ester (27:1/16:1) and diacylglycerol (16:0_18:2) elevations may increase anorexia nervosa (AN) risk, while sphingomyelin (d36:2) elevation potentially lowers it. LDSC analysis showed no substantial genetic link between the three lipids and AN, while low posterior probability of hypothesis 4 from COLOC test disputed the presence of shared variants. Besides, AN risk elevated by sterol ester's (27:1/16:1) was suggested to mediate through C-X-C chemokine 10 downregulation. In the reverse MR, we uncovered varied causal ties: ADHD increased sterol ester (27:1/20:3), phosphatidylcholines (18:0_20:3, 18:1_20:3); Alzheimer's disease lowered phosphatidylcholine (O - 18:1_20:3); Ischemic stroke tied to less phosphatidylcholine (16:0_0:0); Obsessive-compulsive disorder exhibited a dual effect, upregulating phosphatidylcholine (16:1_18:0) and downregulating sterol ester (27:1/22:6); Parkinson's disease linked to less diacylglycerol (18:1_18:3); Schizophrenia tied to more triacylglycerols (48:0,51:1); Migraine reduced sterol ester (27:1/20:2). These insights reveal causal dynamics between plasma lipids and neuropsychiatric conditions. Our findings extend the causal landscape linking the plasma lipidome to NPDs, offering insights for the discovery of novel biomarkers and therapeutic targets in these diseases.

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来源期刊
Molecular Neurobiology
Molecular Neurobiology 医学-神经科学
CiteScore
9.00
自引率
2.00%
发文量
480
审稿时长
1 months
期刊介绍: Molecular Neurobiology is an exciting journal for neuroscientists needing to stay in close touch with progress at the forefront of molecular brain research today. It is an especially important periodical for graduate students and "postdocs," specifically designed to synthesize and critically assess research trends for all neuroscientists hoping to stay active at the cutting edge of this dramatically developing area. This journal has proven to be crucial in departmental libraries, serving as essential reading for every committed neuroscientist who is striving to keep abreast of all rapid developments in a forefront field. Most recent significant advances in experimental and clinical neuroscience have been occurring at the molecular level. Until now, there has been no journal devoted to looking closely at this fragmented literature in a critical, coherent fashion. Each submission is thoroughly analyzed by scientists and clinicians internationally renowned for their special competence in the areas treated.
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