摘要
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2227例病例和454121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=0.9005,95%CI:0.8109-1.0000,P=0.0499)、磷脂酰肌醇(18:0/18:2,OR=0.8954,95%CI:0.8089-0.9912,P=0.0332)和磷脂酰胆碱(16:0/20:2,OR=0.9183,95%CI:0.8458-0.9971,P=0.0425)与膝骨关节炎呈负相关,磷脂酰胆碱(O-16:0/18:2,OR=1.2219,95%CI:0.9098-1.6410,P=0.1987)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。
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 2227 cases and 454121 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 r^(2)<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=0.9005,95%CI:0.8109-1.0000,P=0.0499),phosphatidylinositol(18:0/18:2,OR=0.8954,95%CI:0.8089-0.9912,P=0.0332),and phosphatidylcholine(16:0/20:2,OR=0.9183,95%CI:0.8458-0.9971,P=0.0425)were negatively correlated with knee osteoarthritis,while phosphatidylcholine(O-16:0/18:2,OR=1.2219,95%CI:0.9098-1.6410,P=0.1987)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.
作者
虞跃跃
张旭
刘艺威
孟梓涵
郝心悦
田春雨
李继安
张一昕
Yu Yueyue;Zhang Xu;Liu Yiwei;Meng Zihan;Hao Xinyue;Tian Chunyu;Li Ji’an;Zhang Yixin(Hebei University of Chinese Medicine,Shijiazhuang 050200,Hebei Province,China;North China University of Science and Technology,Tangshan 063210,Hebei Province,China;Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications,Tangshan 063210,Hebei Province,China)
出处
《中国组织工程研究》
北大核心
2026年第18期4763-4770,共8页
Chinese Journal of Tissue Engineering Research
基金
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。
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
knee osteoarthritis
lipid types
Mendelian randomization
genetic variation
causal relationship
diacylglycerol
phosphatidylinositol
phosphatidylcholine
