类风湿性关节炎与骨质疏松症和骨密度关系的孟德尔随机化分析  

Mendelian randomization study on the association between rheumatoid arthritis and osteoporosis and bone mineral density

作　　者：武瑞骐 周毅 夏天[1] 张驰 杨启培 张璇 张亚忠 崔伟[1] Wu Ruiqi;Zhou Yi;Xia Tian;Zhang Chi;Yang Qipei;Zhang Xuan;Zhang Yazhong;Cui Wei(Ruikang Hospital,Guangxi University of Chinese Medicine,Nanning 530000,Guangxi Zhuang Autonomous Region,China;Guangxi University of Chinese Medicine,Nanning 530299,Guangxi Zhuang Autonomous Region,China;Department of Orthopedics,Wuzhou Hospital of Traditional Chinese Medicine,Wuzhou 543000,Guangxi Zhuang Autonomous Region,China)

机构地区：[1]广西中医药大学附属瑞康医院,广西壮族自治区南宁市530000 [2]广西中医药大学,广西壮族自治区南宁市530299 [3]梧州市中医医院骨科,广西壮族自治区梧州市543000

出　　处：《中国组织工程研究》2024年第23期3715-3721,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金资助项目(81960803),项目参与人:张驰;广西壮族自治区临床重点专科(创伤外科)建设项目[部门预算社(2021)],项目参与人:张驰;广西自然科学基金项目(2023GXNSFAA026075),项目参与人:张驰;广西自然科学基金青年基金(2020GXNSFBA159053),项目参与人:张驰;广西中医药大学校级博士研究生科研创新项目(YCBXJ2021019),项目负责人:夏天;广西中医药大学青年创新研究团队项目(2021TD001);广西中医药大学桂派中医药传承创新团队(2022A004),项目参与人:夏天;广西中医药适宜技术开发与推广项目(GZSY22-39),项目负责人:夏天;广西中医药适宜技术开发与推广项目(GZSY22-36),项目参与人:张驰。

摘　　要：背景:许多临床研究观察表明类风湿性关节炎与骨质疏松症和骨密度之间存在密切关系,但类风湿性关节炎与骨质疏松症和骨密度之间是否存在因果遗传尚不清楚。目的:采用两样本孟德尔随机化研究方法评估类风湿性关节炎与骨质疏松症和骨密度之间潜在的因果关系,从遗传学的角度对潜在的机制提供有意义的见解,为早期预防骨质疏松症、改善疾病的发生发展提供参考。方法:从全基因组关联研究(GWAS)公开数据库中筛选出与类风湿性关节炎相关的(P<5×10^(-8))单核苷酸多态性位点作为工具变量。研究结局主要包括骨质疏松症、5个不同部位的骨密度,包括全身骨密度、腰椎骨密度、股骨颈骨密度、足跟骨密度以及前臂骨密度。逆方差加权法为该研究评估因果效应的主要分析方法,文章采用加权中位数法、简单中位数法、加权中值方法和MR-Egger回归用于补充说明,以比值比(OR)和95%可信区间(95%CI)评价类风湿性关节炎与骨质疏松症及骨密度风险之间的因果关系,使用类风湿性关节炎Cochran’s Q检验异质性,利用MR-Egger-intercept检验是否存在水平多效性。结果与结论:①逆方差加权法结果表明遗传预测的类风湿性关节炎与骨质疏松症呈正相关(OR=1.123,95%CI:1.077-1.171,P=4.02×10^(-8)),异质性检验表明单核苷酸多态性位点不存在异质性(P=0.388),MR-Egger-intercept检验未检测到水平多效性(P=0.571),敏感性分析显示研究结果没有产生偏倚。②类风湿性关节炎与5个部位的骨密度之间不存在因果关系显示如下:全身骨密度(OR=1.000,95%CI:0.988-1.012,P=0.925)、腰椎骨密度(OR=0.999,95%CI:0.982-1.016,P=0.937)、股骨颈骨密度(OR=1.001,95%CI:0.986-1.016,P=0.866)、足跟骨密度(OR=0.996,95%CI:0.989-1.004,P=0.419)、前臂骨密度(OR=1.063,95%CI:0.970-1.031,P=0.996)。MR-Egger-intercept分析未检测到潜在的水平多效性(全身骨密度:P=0.253;腰椎�BACKGROUND:Many clinical research observations have indicated a close association between rheumatoid arthritis and osteoporosis as well as bone mineral density(BMD).However,it remains unclear whether there is a causal genetic relationship between rheumatoid arthritis and the development of osteoporosis and alterations of BMD.OBJECTIVE:To assess the potential causal relationship between rheumatoid arthritis and osteoporosis as well as BMD using a two-sample Mendelian randomization approach,provide meaningful insights from a genetic perspective into the underlying mechanisms and offer a reference for early prevention of osteoporosis and improvement in the progression of the disease.METHODS:We conducted a study using data from publicly available genome-wide association studies databases to identify single nucleotide polymorphisms associated with rheumatoid arthritis as instrumental variables(P<5×10^(-8)).The main outcomes of the study included osteoporosis and BMD at five different sites,including total body BMD,lumbar spine BMD,femoral neck BMD,heel BMD,and forearm BMD.The inverse variance-weighted method was used as the primary analysis method to evaluate causal effects.Weighted median,simple median,weighted mode and MR-Egger regression were used as supplementary analyses.Causal relationships between rheumatoid arthritis and the risk of osteoporosis and BMD were assessed using odds ratios(OR)and 95%confidence intervals(CI).Heterogeneity was assessed using Cochran’s Q test and horizontal pleiotropy was evaluated using MR-Egger intercept tests.RESULTS AND CONCLUSION:The inverse variance-weighted analysis demonstrated a positive association between genetically predicted rheumatoid arthritis and osteoporosis(OR=1.123,95%CI:1.077-1.171;P=4.02×10^(-8)).Heterogeneity test(P=0.388)indicated no significant heterogeneity among the single nucleotide polymorphisms.MR-Egger intercept(P=0.571)tests did not detect horizontal pleiotropy,and sensitivity analysis showed no evidence of bias in the study results.There was no caus

关 键 词：骨质疏松症 类风湿性关节炎 骨密度 孟德尔随机化 单核苷酸多态性 因果关联 全基因组关联研究 工具变量 

分 类 号：R44[医药卫生—诊断学] R318[医药卫生—临床医学] R684