摘要
目的:依托英国生物样本库(UK Biobank)数据,探讨血浆蛋白与冠心病发病风险的关联。方法:应用Cox比例风险模型评估2911种蛋白质与冠心病发病的前瞻性关联,结合通路富集分析揭示生物学过程。通过双样本孟德尔随机化、共定位分析推断因果关系,并依据DrugBank数据库评估关键蛋白的临床转化潜力。结果:经过中位14.52年的随访,共观察到3760例新发冠心病病例。共识别出508种蛋白质与冠心病风险显著相关,且富集于动脉粥样硬化相关通路。孟德尔随机化分析进一步鉴定出27种与冠心病存在因果关系的蛋白质,共定位分析支持PCSK9和IFI30蛋白与冠心病共享因果遗传变异。药物靶点验证提示部分蛋白具有已知的药理开发基础。结论:本研究明确了与冠心病风险相关的关键血浆蛋白及其因果作用,为阐明疾病机制、开发早期预测模型与精准治疗策略提供理论基础。
Objective:To investigate the association between plasma proteins and coronary artery disease(CAD)risk using data from the UK Biobank.Methods:Cox proportional hazards models were applied to assess prospective associations of 2,911 proteins with CAD incidence.Pathway enrichment analysis was performed to identify relevant biological processes.Two-sample Mendelian randomization(MR)and colocalization analyses were conducted to infer causal relationships,and the clinical translational potential of key proteins was evaluated using DrugBank databases.Results:During a median follow-up of 14.52 years,3,760 incident CAD cases were documented.A total of 508 proteins were identified to be significantly associated with the risk of CAD,and these proteins were enriched in atherosclerosis-related pathways.MR analysis confirmed 27 proteins with causal evidence for CAD.Colocalization analysis supported shared causal genetic variants between CAD and PCSK9/IFI30 proteins.Drug target validation indicated existing pharmacological development potential for several proteins.Conclusion:This study identifies key plasma proteins associated with CAD risk and demonstrates their causal roles,providing a theoretical foundation for elucidating disease mechanisms and developing early prediction models and precision treatment strategies.
作者
吴勤婷
黄代政
WU Qinting;HUANG Daizheng(Life Sciences Institute,School of Life Sciences and Medical Engineering,Guangxi Medical University,Nanning 530021,China)
出处
《广西医科大学学报》
2025年第6期861-869,共9页
Journal of Guangxi Medical University
基金
广西重点研发计划项目(No.桂科AB20072003)。
关键词
血浆蛋白
冠心病
队列研究
孟德尔随机化
共定位分析
药物靶点
plasma proteins
coronary artery disease
cohort study
Mendelian randomization
colocalization analysis
drug target
