首页|血清代谢物和三叉神经痛的综合双样本孟德尔随机化分析

血清代谢物和三叉神经痛的综合双样本孟德尔随机化分析

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目的 对血清代谢物和三叉神经痛间可能因果关系进行全面梳理和研究,为三叉神经痛患者后续治疗和管理提供新思路.方法 通过全基因组关联研究数据库和芬兰数据库FINNGEN R10分别获取血清代谢物和三叉神经痛的全基因组关联研究(GWASs)的总结数据,以48 6种血清代谢物作为暴露因素,以三叉神经痛作为结局,进行双样本孟德尔随机化(MR)研究,探讨血清代谢物与三叉神经痛的因果效应.逆方差加权法(IVW)分析作为因果估计方法,并伴随着一系列敏感性分析以评估结果的稳健性.此外,使用基于网络的MetaboAnalyst进行代谢通路分析.P<0.05为差异有统计学意义.结果 在校正假发现率(FDR)后,MR分析结果显示与7种代谢物存在显着的因果关系,即磷酸盐(OR=0.00,95%CI:0.00~0.05),苯甲酸(OR=4.34,95%CI:1.86~10.11),1-硬脂酰甘油磷酸肌醇(OR=3.18,95%CI:1.93~5.24),棕榈酰肉碱(OR=0.15,95%CI:0.05~0.44),焦谷氨酰甘氨酸(OR=2.13,95%CI:1.39~3.27),10-十七 烯酸酯(OR=4.33,95%CI:2.11~8.88),4-乙烯基苯酚硫酸盐(OR=2.15,95%CI:1.46~3.15).但在进一步敏感性分析后,未发现特定代谢物通过了所有敏感性测试,所有代谢物的Cochran Q检验均发现异质性.7种代谢物通过了两种敏感性测试,即MR-Egger截距测试与留一法分析,因此被认为是稳健的.此外,通过对7种代谢物进行代谢途径富集分析确定了 44条与三叉神经痛表型相关的代谢途径,其中P<0.01的有三条,分别为:硫胺素代谢,乳糖降解,三酰基甘油生物合成.结论 7种代谢物及其相关代谢途径可能与三叉神经痛存在因果关联,这将有助于三叉神经痛的诊断和治疗.
Comprehensive two-sample mendelian randomization analysis of serum metabolites and trigeminal neural-gia
Objective To comprehensively investigate and study the possible causal relationship between serum metabolites and trigeminal neuralgia,providing new ideas for subsequent treatment and management of patients with trigeminal neuralgia.Methods Summarized data of Genome-Wide Association Studies(GWASs)of serum metabolites and trigeminal neuralgia were obtained from the Genome-Wide Association Study(GWAS)Catalog and the Finnish database FINNGEN R10.With 486 serum metabolites as exposure factors and trigeminal neuralgia as the outcome,a two-sample Mende-lian randomization(MR)study was conducted to explore the causal effect of serum metabolites on tri-geminal neuralgia.The inverse variance weighted(1VW)method was used as the causal estimation method,accompanied by a series of sensitivity analyses to assess the robustness of the results.In addi-tion,MetaboAnalyst based on network analysis was used for metabolic pathway analysis.P<0.05 was considered as statistically significant.Results After correcting for false discovery rate(FDR),the MR analysis results showed significant causal relationships with 7 metabolites,namely phosphate(OR=0.00,95%CI:0.00-0.05),benzoic acid(OR=4.34,95%CI:1.86-10.11),1-stearoyl-glycerophos-phoinositol(OR=3.18,95%CI:1.93-5.24),palmitoylcarnitine(OR=0.15,95%CI:0.05-0.44),py-roglutamylglycine(OR=2.13,95%CI:1.39-3.27),10-heptadecenoate(OR=4.33,95%CI:2.11-8.88),and 4-vinylphenol sulfate(OR=2.15,95%CI:1.46-3.15).However,after further sensitivity analysis,no specific metabolite passed all sensitivity tests,and heterogeneity was found in Cochran's Q test for all metabolites.Seven metabolites passed two sensitivity tests,namely MR-Egger intercept test and leave-one-out analysis,and were considered robust.In addition,metabolic pathway enrich-ment analysis of the seven metabolites identified 44 metabolic pathways related to the phenotype of tri-geminal neuralgia,of which three had P<0.01:thiamine metabolism,lactose degradation,and tria-cylglycerol biosynthesis.Conclusion Seven metabolites and their related metabolic pathways may have a causal association with trigeminal neuralgia,which will contribute to the diagnosis and treatment of trigeminal neuralgia.

Trigeminal neuralgiaSerum metabolitesMendelian randomizationGenome-wide association studies

王清、甄法萌、李昕、陈佳兴、刘晓卓、范明明、李梅

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华北理工大学临床医学院 河北唐山 063000

华北理工大学附属医院 河北唐山 063000

三叉神经痛 血清代谢物 孟德尔随机化 全基因组关联研究

河北省临床医学优秀人才培养项目河北省中医药科研计划项目河北省医学科学研究课题计划项目唐山市人才资助项目

ZF2023008202242620231264A202110018

2024

华北理工大学学报(医学版)
河北联合大学

华北理工大学学报(医学版)

影响因子:0.569
ISSN:2095-2694
年,卷(期):2024.26(4)