端粒长度与10种常见肌肉骨骼疾病的关系孟德尔随机化分析  

Mendelian randomization study on the association between telomere length and 10 common musculoskeletal diseases

作　　者：罗伟东[1] 蒲彬 古鹏 黄枫[1] 郑晓辉[1] 陈福洪 Luo Weidong;Pu Bin;Gu Peng;Huang Feng;Zheng Xiaohui;Chen Fuhong(The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510000,Guangdong Province,China;The First Clinical Medical College of Guangzhou University of Chinese Medicine,Guangzhou 510000,Guangdong Province,China;Department I of Orthopedics,Suining Municipal Hospital of Traditional Chinese Medicine Hospital,North Sichuan Medical College,Suining 629000,Sichuan Province,China)

机构地区：[1]广州中医药大学第一附属医院,广东省广州市510000 [2]广州中医药大学第一临床医学院,广东省广州市510000 [3]川北医学院附属遂宁市中医医院骨一科,四川省遂宁市629000

出　　处：《中国组织工程研究》2025年第3期654-660,共7页Chinese Journal of Tissue Engineering Research

基　　金：广州市科技计划项目(202201020267),项目负责人:罗伟东;国家中医药名家工作室建设项目(黄枫工作室N75,2022年),项目负责人:黄枫;四川省遂宁市中医药管理局科学技术研究专项课题(SN2021B11),项目负责人:陈福洪。

摘　　要：背景:多项观察性研究表明,端粒长度与肌肉骨骼疾病之间存在潜在的关联,然而它们之间的潜在机制仍不清楚。目的:利用两样本孟德尔随机化分析来探索端粒长度与肌肉骨骼疾病之间的遗传因果关系。方法:从英国生物银行中获得端粒长度的全基因组关联研究汇总数据。从FinnGen财团中获得了关于10种常见肌肉骨骼疾病(骨坏死、骨髓炎、骨质疏松、类风湿关节炎、腰痛、椎管狭窄、痛风、肩周炎、强直性脊柱炎和下肢深静脉血栓)的全基因组关联研究汇总数据。使用逆方差加权、孟德尔随机化-Egger和加权中位数方法评估端粒长度与10种肌肉骨骼疾病的因果关系,逆方差加权作为主要的孟德尔随机化分析方法,并进行敏感性分析探讨结果稳健性。结果与结论:①逆方差加权法结果表明,遗传预测的端粒长度与类风湿关节炎(OR=0.78,95%CI:0.64-0.95,P=0.015)和骨坏死(OR=0.56,95%CI:0.36-0.90,P=0.016)风险之间存在负向因果关系,但未发现端粒长度与其他8种肌肉骨骼疾病之间存在因果关系(P均>0.05)。②敏感性分析结果表明因果关系稳健,孟德尔随机化-Egger截距分析未检测到潜在的水平多效性(P均>0.05)。③此项孟德尔随机化研究支持端粒长度对类风湿关节炎和骨坏死的保护作用的结论,然而,未来将需要更多的基础和临床研究来验证。BACKGROUND:Multiple observational studies have suggested a potential association between telomere length and musculoskeletal diseases.However,the underlying mechanisms remain unclear.OBJECTIVE:To investigate the genetic causal relationship between telomere length and musculoskeletal diseases using two-sample Mendelian randomization analysis.METHODS:Genome-wide association study summary data of telomere length were obtained from the UK Biobank.Genome-wide association study summary data of 10 common musculoskeletal diseases(osteonecrosis,osteomyelitis,osteoporosis,rheumatoid arthritis,low back pain,spinal stenosis,gout,scapulohumeral periarthritis,ankylosing spondylitis and deep venous thrombosis of lower limbs)were obtained from the FinnGen consortium.Inverse variance weighting,Mendelian randomization-Egger and weighted median methods were used to evaluate the causal relationship between telomere length and 10 musculoskeletal diseases.Inverse variance weighting was the primary Mendelian randomization analysis method,and sensitivity analysis was performed to explore the robustness of the results.RESULTS AND CONCLUSION:(1)Inverse variance-weighted results indicated a negative causal relationship between genetically predicted telomere length and rheumatoid arthritis(odds ratio=0.78,95%confidence interval:0.64-0.95,P=0.015)and osteonecrosis(odds ratio=0.56,95%confidence interval:0.36-0.90,P=0.016).No causal relationship was found between telomere length and the other eight musculoskeletal diseases(all P>0.05).(2)Sensitivity analysis affirmed the robustness of these causal relationships,and Mendelian randomization-Egger intercept analysis found no evidence of potential horizontal pleiotropy(all P>0.05).(3)This Mendelian randomized study supports that telomere length has protective effects against rheumatoid arthritis and osteonecrosis.However,more basic and clinical research will be needed to support our findings in the future.

关 键 词：端粒长度 肌肉骨骼疾病 孟德尔随机化 全基因组关联研究 单核苷酸多态性 因果关系 工具变量 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R68