中国实用神经疾病杂志2026，Vol.29Issue(1)：7-13,7.DOI:10.12083/SYSJ.250333
血浆蛋白与自主神经功能失调的因果关联:一项孟德尔随机化研究
Causal relationship between plasma proteins and autonomic dysfunction:A Mendelian randomization study
摘要
Abstract
Objective To investigate the causal relationship between plasma proteins and autonomic dysfunction(AD).Methods Plasma protein data and AD Genome-Wide Association Study(GWAS)datasets were acquired from the FinnGen consortium.Two-sample Mendelian randomization(MR)analysis was performed using inverse-variance weighted,MR-Egger,and weighted median methods to evaluate potential causal associations.Bidirectional MR analysis examined reverse causation possibilities.Sensitivity analyses including Cochran's Q test,MR-Egger intercept test,and MR-PRESSO global test were implemented to verify result robustness.Functional characterization of identified proteins was conducted through Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis and gene ontology(GO)annotation.Results Forward MR analysis identified 177 plasma proteins showing nominal associations with AD risk(P＜0.05).Reverse MR analysis demonstrated no significant reverse causation(P＞0.05).Sensitivity analysis confirmed the absence of horizontal pleiotropy.After Bonferroni correction,5 proteins maintained significant associations:mannose receptor C-type 1(MRC1),complement factor B(CFB),procollagen C-endopeptidase enhancer 2(PCOLCE2),cluster of differentiation 14(CD 14),and cathepsin D(CTSD).Conclusion This study establishes novel causal relationships between specific plasma proteins and AD pathogenesis,providing mechanistic insights for potential therapeutic targeting.The identified proteins implicate complement activation and extracellular matrix remodeling pathways in AD development.关键词
自主神经功能失调/血浆蛋白质组学/孟德尔随机化/神经系统疾病/因果联系Key words
Autonomic dysfunction/Plasma proteomics/Mendelian randomization/Nervous system disor-ders/Causal connection分类
医药卫生引用本文复制引用
李晋峰,虞意华..血浆蛋白与自主神经功能失调的因果关联:一项孟德尔随机化研究[J].中国实用神经疾病杂志,2026,29(1):7-13,7.基金项目
浙江省医药卫生科技计划项目(编号:2023KY433) （编号:2023KY433）
