免疫细胞介导不同脂质与膝骨关节炎的相关性:欧洲个体全基因组关联分析  

Immune cells mediate the association between different lipids and knee osteoarthritis:a genome-wide association analysis of European individuals

作　　者：霍将[1] 丁宇 原杰 Huo Jiang;Ding Yu;Yuan Jie(Department of Orthopedics,The Second Hospital of Shanxi Medical University,Taiyuan 030001,Shanxi Province,China;Shanxi Provincial Integrated TCM and WM Hospital,Taiyuan 030001,Shanxi Province,China)

机构地区：[1]山西医科大学第二医院骨科,山西省太原市030001 [2]山西省中西医结合医院,山西省太原市030001

出　　处：《中国组织工程研究》2025年第18期3934-3940,共7页Chinese Journal of Tissue Engineering Research

基　　金：山西省基础研究计划自由探索类青年研究项目(202203021212053),项目负责人:霍将;山西省基础研究计划自由探索类青年研究项目(20210302124670),项目负责人:原杰;山西省高等教育“百亿工程”科技引导专项(BYJL031),项目参与人:原杰。

摘　　要：背景:观察性研究发现脂质与免疫细胞对于骨关节炎进展具有双重影响,但其具体作用机制尚不清楚。目的:探究脂质与膝骨关节炎的因果关系是否受免疫细胞调控。方法:179种脂质来源于Linda Ottensman数据库,从Open GWAS上获取到了731种免疫细胞相关的单核苷酸多态性作为工具变量,膝骨关节炎的全基因组关联研究数据来自于骨关节炎遗传学联盟。首先采用双样本孟德尔随机化方法从遗传学角度分别探讨脂质与膝骨关节炎、免疫细胞与膝骨关节炎、脂质与免疫细胞的因果关系。另外采用贝叶斯加权孟德尔随机化验证脂质与膝骨关节炎的因果关系,反向孟德尔随机化和Steiger方向性检验评估正向关系。随后进行敏感性分析,包括Cochran’s Q检验消除异质性,MR-PRESSO全局检验和MR-Egger截距排除水平多效性,留一法评估单个单核苷酸多态性驱动因素对随机估计的影响。最后,通过两步孟德尔随机化方法确定特定免疫细胞性状在脂质与膝骨关节炎因果关系中的中介效应。结果与结论:①逆方差加权法和贝叶斯加权算法共同确定8种与膝骨关节炎存在因果关系的脂质种类;②Cochran’s Q、MR-PRESSO和MR-Egger截距结果均无统计学意义(P<0.05);③同时共计算得出了3组中介关系,介导比例最低为11.85%,最高为45.48%;④提示免疫细胞水平在脂质与膝骨关节炎的调节进程中发挥潜在作用,这一发现能为深入探索膝骨关节炎的作用机制提供新的视角。BACKGROUND:Observational studies have found a dual effect of lipids and immune cells on osteoarthritis progression,but the exact mechanism of action is not yet clear.OBJECTIVE:To investigate whether the causal relationship between lipids and knee osteoarthritis is regulated by immune cells.METHODS:179 lipids were obtained from the Linda Ottensman database,731 immune cell-associated single nucleotide polymorphisms were obtained from Open GWAS as instrumental variables,and genome-wide association data for knee osteoarthritis were obtained from the Osteoarthritis Genetics Consortium.First,we used a two-sample Mendelian randomization method to investigate the causal relationships between lipids and knee osteoarthritis,between immune cells and knee osteoarthritis,and between lipids and immune cells from a genetic perspective.In addition,Bayesian-weighted Mendelian randomization verified the causal relationship between lipids and knee osteoarthritis,and reverse Mendelian randomization and Steiger directionality test assessed the positive relationship.Second,sensitivity analyses were performed,including Cochran’s Q test to eliminate heterogeneity,MR-PRESSO global test and MR-Egger intercept to rule out horizontal pleiotropy,and leave-one-out method to assess the effect of individual single nucleotide polymorphism drivers on random estimates.Finally,the mediating effect of specific immune cell traits in the causal relationship between lipids and knee osteoarthritis was determined by a twostep Mendelian randomization method.RESULTS AND CONCLUSION:The inverse variance weighting method and Bayesian-weighted algorithm together identified eight lipid species that were causally associated with knee osteoarthritis.The results of Cochran’s Q,MR-PRESSO,and MR-Egger intercept were not statistically significant(P<0.05).Meanwhile,a total of three sets of mediated relationships were calculated,with the lowest mediation percentage of 11.85%and the highest of 45.48%.These findings indicate the level of immune cells plays a potentia

关 键 词：脂质 膝骨关节炎 孟德尔随机化 免疫细胞 中介分析 因果关系 工程化组织构建 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R580