2型糖尿病对各年龄段全身骨密度影响的两样本孟德尔随机化分析  

Effect of type 2 diabetes mellitus on bone mineral density in different age groups:a two-sample Mendelian randomization study

作　　者：黄文茁 向海珠 马玮玮 黄新 付红军 熊勇[1] Huang Wenzhuo;Xiang Haizhu;Ma Weiwei;Huang Xin;Fu Hongjun;Xiong Yong(Hubei University of Chinese Medicine,Wuhan 430061,Hubei Province,China;Xiangyang Hospital of Traditional Chinese Medicine,Xiangyang 441001,Hubei Province,China)

机构地区：[1]湖北中医药大学,湖北省武汉市430061 [2]襄阳市中医医院,湖北省襄阳市441001

出　　处：《中国组织工程研究》2024年第35期5662-5668,共7页Chinese Journal of Tissue Engineering Research

摘　　要：背景:流行病学研究显示2型糖尿病与骨密度存在相关性,但两者间的因果关联以及是否与年龄有关仍是未知。目的:基于孟德尔随机化技术研究2型糖尿病与不分年龄段及各年龄段全身骨密度的相关性。方法:从布里斯托尔大学的IEU GWAS数据库中选择2型糖尿病与各年龄段骨密度的GWAS数据,其中暴露数据集中获取与2型糖尿病具有显著相关性的单核苷酸多态性(single nucleotide polymorphism,SNP)作为工具变量,将各年龄段骨密度选定为结局变量,采用逆方差加权法、加权中位数法以及MR-Egger回归进行2型糖尿病与骨密度的两样本孟德尔随机化分析,以β值来评价2型糖尿病与各年龄段骨密度之间的因果关系。结果与结论:(1)从GWAS汇总数据共提取118个SNP作为工具变量,MR-Egger回归结果显示不存在水平多效性,但存在异质性,因此研究以逆方差加权法结果为准。(2)逆方差加权法结果显示,2型糖尿病可能是骨密度的潜在保护性因素,且与年龄存在相关性[未指定年龄骨密度(β=0.038,95%CI:1.01-1.07,P=0.002),>60岁骨密度(β=0.052,95%CI:1.01-1.09,P=0.027),>45-60岁骨密度(β=0.049,95%CI:1.01-1.09,P=0.009),>30-45岁骨密度(β=0.033,95%CI:0.99-1.07,P=0.127),>15-30岁骨密度(β=0.025,95%CI:0.95-1.10,P=0.506),0-15岁骨密度(β=0.006,95%CI:0.96-1.04,P=0.716)]。MR-Egger回归及加权中位数也有类似结果。(3)结果表明2型糖尿病可能是骨密度的保护性因素之一,且与年龄存在相关性。BACKGROUND:Epidemiologic studies have shown a correlation between type 2 diabetes mellitus and bone mineral density,but the causal association between the two and whether it is age-related remains unknown.OBJECTIVE:To study the correlation between type 2 diabetes mellitus and whole body bone mineral density at unspecified age and at all ages based on the Mendelian randomization technique.METHODS:The genome-wide association study(GWAS)data of type 2 diabetes mellitus and bone mineral density at all ages were selected from the IEU GWAS database of the University of Bristol.The exposure data were single nucleotide polymorphisms with significant correlation with type 2 diabetes mellitus as instrumental variables,and bone mineral density at all ages was selected as the outcome variable.Two-sample Mendelian randomization analysis of type 2 diabetes mellitus and bone mineral density was performed using inverse variance weighted method,weighted median estimator,and MR-Egger regression.Theβvalue was used to evaluate the causal relationship between type 2 diabetes mellitus and bone mineral density at all ages.RESULTS AND CONCLUSION:A total of 118 single nucleotide polymorphisms were extracted from the GWAS summary data as instrumental variables.The MR-Egger regression results showed that there was no horizontal pleiotropy,but there was heterogeneity.Therefore,this study was based on the inverse variance weighted results.Inverse variance weighted results showed that type 2 diabetes mellitus may be a potential protective factor for bone mineral density and is associated with age:age-unspecified bone mineral density[β=0.038,95%confidence interval(CI):1.01-1.07,P=0.002],bone mineral density over 60 years old(β=0.052,95%CI:1.01-1.09,P=0.027),bone mineral density between 45-60 years old(β=0.049,95%CI:1.01-1.09,P=0.009),bone mineral density between 30-45 years old(β=0.033,95%CI:0.99-1.07,P=0.127).bone mineral density of 15-30 years old(β=0.025,95%CI:0.95-1.10,P=0.506),bone mineral density of 0-15 years old(β=0.006,95%CI:0.

关 键 词：孟德尔随机化 2型糖尿病 骨密度 因果推断 单核苷酸多态性 

分 类 号：R496[医药卫生—康复医学] R318[医药卫生—临床医学] R681