外周血细胞与骨质疏松症的因果关系  

Causal relationship between peripheral blood cells and osteoporosis

作　　者：刘科第 陈勇喜[2] 覃海飚[2] 郭圣挥 覃忠设 蒙觉威 崔善林 范俊鸿 Liu Kedi;Chen Yongxi;Qin Haibiao;Guo Shenghui;Qin Zhongshe;Meng Juewei;Cui Shanlin;Fan Junhong(Graduate School of Guangxi University of Chinese Medicine,Nanning 530003,Guangxi Zhuang Autonomous Region,China;The First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530003,Guangxi Zhuang Autonomous Region,China)

机构地区：[1]广西中医药大学研究生学院,广西壮族自治区南宁市530003 [2]广西中医药大学第一附属医院,广西壮族自治区南宁市530003

出　　处：《中国组织工程研究》2025年第12期2605-2613,共9页Chinese Journal of Tissue Engineering Research

基　　金：广西中医药适宜技术开发与推广项目(GZSY-23-28),项目负责人:陈勇喜;广西中医药大学校级科研项目(2022MS043),项目负责人:陈勇喜。

摘　　要：背景:流行病学调查和一些实验表明,外周血细胞和骨质疏松症存在密切关系,但两者在遗传学层面上的因果关系尚不清楚。目的:运用孟德尔随机化探究外周血细胞和骨质疏松症的因果关系。方法:从BCX、MRC-IEU等数据库分别获取外周血细胞、不同年龄段全身骨密度、跟骨骨密度的GWAS数据集,将血细胞作为暴露数据,不同年龄段骨密度及跟骨骨密度作为结局数据,使用逆方差加权法、MR-Egger、加权中值法、加权中位数、简单中位数等方法进行孟德尔随机化分析,使用Cochran’s Q、MR-Egger回归、Leave-one-out法等检验对结果进行异质性、多效性和敏感性评估,用β值评估暴露与结局的因果关系。结果与结论:①因Cochran’s Q结果显示孟德尔随机化结果存在异质性,故研究结果以逆方差加权法结果为标准。逆方差加权结果显示:当不同年龄段骨密度作为结局时,白细胞计数与(45-60岁)全身骨密度呈负向因果关系(β=-0.07,95%CI:-0.13,-0.01,P=0.02),单核细胞计数与(45-60岁)全身骨密度呈正向因果关系(β=0.05,95%CI:0.00,0.10,P=0.037),白细胞计数、嗜碱性粒细胞计数与(>60岁)全身骨密度呈负向因果关系(β=-0.04,95%CI:-0.07,-0.01,P=0.005;β=-0.04,95%CI:-0.07,-0.00,P=0.038),血红蛋白浓度及红细胞压积与(>60岁)全身骨密度呈正向因果关系(β=0.04,95%CI:0.01,0.08,P=0.012;β=0.04,95%CI:0.00,0.07,P=0.039),白细胞计数与(未区分年龄段)全身骨密度呈负向因果关系(β=-0.10,95%CI:-0.16,-0.03,P=0.002);当跟骨骨密度作为结局时,白细胞计数与跟骨骨密度呈负向因果关系(β=-0.04,95%CI:-0.07,-0.01,P=0.016),血红蛋白浓度、红细胞压积与跟骨骨密度呈正向因果关系(β=0.05,95%CI:0.01,0.08,P=0.007;β=0.05,95%CI:0.01,0.08,P=0.004)。②为保证结果稳健性,将外周血细胞与不同年龄段全身骨密度、跟骨骨密度的孟德尔随机化结果进行Meta分析,结果提示对数变换后的白细胞�BACKGROUND:Epidemiologic investigations and some experiments have shown that there is a close relationship between peripheral blood cells and osteoporosis,but the causal relationship between the two at the genetic level is still unclear.OBJECTIVE:To explore the causal relationship between peripheral blood cells and osteoporosis using Mendelian randomization methods.METHODS:Genome-wide association study data sets on peripheral blood cells,overall bone density at different ages,and calcaneal bone density were obtained from databases such as Blood Cell Consortium and MRC Integrative Epidemiology Unit.Blood cells were used as exposure data,with bone density at different ages and calcaneal bone density serving as outcome data.Mendelian randomization analyses were performed using methods such as inverse variance weighting,MR-Egger,weighted median method,and simple median.The results were assessed for heterogeneity,pleiotropy,and sensitivity using Cochran’s Q,MR-Egger regression,and Leave-one-out method.The causal relationship between exposure and outcomes was evaluated usingβvalues.RESULTS AND CONCLUSION:Due to the heterogeneity revealed by Cochran’s Q test in the Mendelian randomization results,the results of the study were based on the inverse variance weighting method.The inverse variance weighting results showed that when age-specific bone density was used as an outcome,there was a negative causal relationship between white blood cell count and whole-body bone mineral density at the age of 45-60 years[β=-0.07,95%confidence interval(CI):-0.13,-0.01,P=0.02],a positive causal relationship between monocyte count and whole-body bone mineral density at the age of 45-60 years(β=0.05,95%CI:0.00,0.10,P=0.037),a negative causal relationship between white blood cell and basophil counts and whole-body bone mineral density over 60 years old(β=-0.04,95%CI:-0.07,-0.01,P=0.005;β=-0.04,95%CI:-0.07,-0.00,P=0.038),a positive causal relationship between hemoglobin concentration and hematocrit and whole-body bone mineral densi

关 键 词：孟德尔随机化 骨质疏松症 骨密度 外周血细胞 因果关系 

分 类 号：R459.9[医药卫生—治疗学] R319[医药卫生—临床医学] R681.53