中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (18): 4763-4770.doi: 10.12307/2026.741

• 组织工程相关大数据分析 Big data analysis in tissue engineering • 上一篇    下一篇

脂质类型与膝骨关节炎：欧洲人群全基因组关联分析

虞跃跃1，2，张  旭2，刘艺威2，孟梓涵2，郝心悦3，田春雨2，4，李继安2，4，张一昕1   

  1. 1河北中医药大学，河北省石家庄市  050200；2华北理工大学，河北省唐山市  063210；3天津中医药大学，天津市  301617；4河北省中西医结合防治糖尿病及其并发症重点实验室，河北省唐山市  063210
  • 收稿日期:2025-07-09 接受日期:2025-09-16 出版日期:2026-06-28 发布日期:2025-12-11
  • 通讯作者: 张一昕，教授，河北中医药大学，河北省石家庄市 067000 共同通讯作者：李继安，教授，华北理工大学，河北省唐山市 063210；河北省中西医结合防治糖尿病及其并发症重点实验室，河北省唐山市 063210
  • 作者简介:虞跃跃，女，1989年生，河北省唐山市人，汉族，河北中医药大学在读博士，副教授，主要从事中医药防治骨性关节炎的机制研究。
  • 基金资助:
    国家科技部对发展中国家科技援助项目(KY01904005)，项目负责人：李继安；河北省国际合作专项(19392507D)，项目负责人：李继安；河北省华北理工大学省属高校基本科研业务费项目(JQN2021034)，项目负责人：虞跃跃

Lipid types and knee osteoarthritis: a genome-wide association study in European populations

Yu Yueyue1, 2, Zhang Xu2, Liu Yiwei2, Meng Zihan2, Hao Xinyue3, Tian Chunyu2, 4, Li Ji’an2, 4, Zhang Yixin1    

  1. 1Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei Province, China; 2North China University of Science and Technology, Tangshan 063210, Hebei Province, China; 3Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; 4Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications, Tangshan 063210, Hebei Province, China
  • Received:2025-07-09 Accepted:2025-09-16 Online:2026-06-28 Published:2025-12-11
  • Contact: Zhang Yixin, Professor, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei Province, China Co-corresponding author: Li Ji’an, Professor, North China University of Science and Technology, Tangshan 063210, Hebei Province, China; Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications, Tangshan 063210, Hebei Province, China
  • About author:Yu Yueyue, PhD candidate, Associate professor, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei Province, China; North China University of Science and Technology, Tangshan 063210, Hebei Province, China
  • Supported by:
    Science and Technology Assistance Program for Developing Countries, Ministry of Science and Technology of China, No. KY01904005 (to LJA); Hebei Provincial International Cooperation Special Project, No. 19392507D (to LJA); Hebei Provincial Basic Research Fund for Provincial Universities, North China University of Technology, No. JQN2021034 (to YYY)

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摘要：


文题释义：
孟德尔随机化：是一种基于遗传变异的因果推断方法，借助基因在减数分裂时随机分配的特性，模拟随机对照试验，以评估暴露与疾病的因果关系。孟德尔随机化分析的核心原理是选择与暴露强相关的遗传变异作为工具变量，并满足3个关键假设。通过分析遗传变异、暴露和结局的关联性，孟德尔随机化推断因果效应避免了传统观察性研究的反向因果和混杂偏倚的影响。该方法为因果推断提供了高效、可靠的遗传学证据。
脂质类型：是指根据化学结构和生物学功能对脂质分子进行的系统性分类。脂质主要包括以下几大类：简单脂质、复合脂质、衍生脂质、活性脂质递质。国际LIPID MAPS数据库采用层次化分类体系，通过精确描述碳链长度、双键位置和立体构型等结构特征，为脂质组学研究提供标准化命名。脂质类型的动态变化与一些疾病的病理过程密切相关，是生物标志物发现和靶向治疗的重要研究对象。

背景：研究表明，不同的脂质类型能够对膝骨关节炎产生影响，但因果关系尚未明确。
目的：基于孟德尔随机化探讨脂质类型与膝骨关节炎之间的因果关系。
方法：使用GWAS Catalog的全基因组关联分析统计数据，179种脂质来源于GeneRISK队列，膝骨关节炎的全基因组关联研究数据包括
2 227例病例和454 121名对照。以单核苷酸多态性作为工具变量，以脂质体显著性阈值P < 1×10-5、膝骨关节炎显著性阈值P < 5×10-6、连锁不平衡阈值r2 < 0.001为条件进行严格筛选，主要采用逆方差加权法进行分析，根据效应指标优势比(OR)及其95%置信区间(CI)评估结果，MR-Egger回归、加权中位数法、简单模式法作为补充分析，并通过留一法分析、异质性检验、多效性检验、反向孟德尔随机化分析等敏感性分析验证结果的稳健性。
结果与结论：二酰基甘油(18∶1/18∶2，OR=0.900 5，95%CI：0.810 9-1.000 0，P=0.049 9)、磷脂酰肌醇(18∶0/18∶2，OR=0.895 4，95%CI：0.808 9-0.991 2，P=0.033 2)和磷脂酰胆碱(16∶0/20∶2，OR=0.918 3，95%CI：0.845 8-0.997 1，P=0.042 5)与膝骨关节炎呈负相关，磷脂酰胆碱(O-16∶0/18∶2，OR=1.221 9，95%CI：0.909 8-1.641 0，P=0.198 7)与膝骨关节炎呈正相关。结果表明，特定脂质可能通过调节炎症或软骨代谢途径影响膝骨关节炎发生风险，为靶向脂质代谢的干预策略提供了遗传学证据。

https://orcid.org/0009-0003-0244-3593(虞跃跃)


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 膝骨关节炎, 脂质类型, 孟德尔随机化, 遗传变异, 因果关系, 二酰基甘油, 磷脂酰肌醇, 磷脂酰胆碱

Abstract: BACKGROUND: Studies have shown that different lipid types can affect knee osteoarthritis, but the causal relationship remains unclear.
OBJECTIVE: To explore the causal relationship between lipid types and knee osteoarthritis using Mendelian randomization.
METHODS: Based on the genome-wide association analysis statistics from the GWAS Catalog, 179 types of lipids were derived from the GeneRISK cohort, and whole genome analysis data for knee osteoarthritis included 2 227 cases and 454 121 controls. Single nucleotide polymorphisms were used as instrumental variables and a strict screening was conducted with a liposome significance threshold of P < 1×10⁻⁵, a knee osteoarthritis significance threshold of P < 5×10−6 and a linkage disequilibrium threshold of r² < 0.001. The inverse variance weighted method was mainly used for analysis. The results were evaluated based on the odds ratio (OR) and its 95% confidence interval (CI). MR-Egger regression, weighted median method, and simple mode method were used as supplementary analyses. The robustness of the results was verified through sensitivity analyses including leave-one-out analysis, heterogeneity test, pleiotropy test, and reverse Mendelian randomization analysis.
RESULTS AND CONCLUSION: Diacylglycerol (18:1/18:2, OR=0.900 5, 95% CI: 0.810 9-1.000 0, P=0.049 9), phosphatidylinositol (18:0/18:2, OR=0.895 4, 95% CI: 0.808 9-0.991 2, P=0.033 2), and phosphatidylcholine (16:0/20:2, OR=0.918 3, 95% CI: 0.845 8-0.997 1, P=0.042 5) were negatively correlated with knee osteoarthritis, while phosphatidylcholine (O-16:0/18:2, OR=1.221 9, 95% CI: 0.909 8-1.641 0, P=0.198 7) was positively correlated with knee osteoarthritis. To conclude, specific lipids may influence the risk of knee osteoarthritis by regulating inflammatory or cartilage metabolic pathways, providing genetic evidence for lipid metabolism-targeted intervention strategies. 


Key words: knee osteoarthritis, lipid types, Mendelian randomization, genetic variation, causal relationship, diacylglycerol, phosphatidylinositol, phosphatidylcholine

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