College of Information Science and Technology, Dalian Maritime University, Dalian, China.
Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
J Bone Miner Res. 2021 Jul;36(7):1281-1287. doi: 10.1002/jbmr.4296. Epub 2021 Apr 5.
Uncovering additional causal clinical traits and exposure variables is important when studying osteoporosis mechanisms and for the prevention of osteoporosis. Until recently, the causal relationship between anthropometric measurements and osteoporosis had not been fully revealed. In the present study, we utilized several state-of-the-art Mendelian randomization (MR) methods to investigate whether height, body mass index (BMI), waist-to-hip ratio (WHR), hip circumference (HC), and waist circumference (WC) are causally associated with two major characteristics of osteoporosis, bone mineral density (BMD) and fractures. Genomewide significant (p ≤ 5 × 10 ) single-nucleotide polymorphisms (SNPs) associated with the five anthropometric variables were obtained from previous large-scale genomewide association studies (GWAS) and were utilized as instrumental variables. Summary-level data of estimated bone mineral density (eBMD) and fractures were obtained from a large-scale UK Biobank GWAS. Of the MR methods utilized, the inverse-variance weighted method was the primary method used for analysis, and the weighted-median, MR-Egger, mode-based estimate, and MR pleiotropy residual sum and outlier methods were utilized for sensitivity analyses. The results of the present study indicated that each increase in height equal to a single standard deviation (SD) was associated with a 9.9% increase in risk of fracture (odds ratio [OR] = 1.099; 95% confidence interval [CI] 1.067-1.133; p = 8.793 × 10 ) and a 0.080 SD decrease of estimated bone mineral density (95% CI -0.106-(-0.054); p = 2.322 × 10 ). We also found that BMI was causally associated with eBMD (beta = 0.129, 95% CI 0.065-0.194; p = 8.113 × 10 ) but not associated with fracture. The WHR adjusted for BMI, HC adjusted for BMI, and WC adjusted for BMI were not found to be related to fracture occurrence or eBMD. In conclusion, the present study provided genetic evidence for certain causal relationships between anthropometric measurements and bone mineral density or fracture risk. © 2021 American Society for Bone and Mineral Research (ASBMR).
当研究骨质疏松症的机制和预防骨质疏松症时，揭示其他因果临床特征和暴露变量非常重要。直到最近，人体测量学与骨质疏松症之间的因果关系还没有被完全揭示。在本研究中，我们利用几种最新的孟德尔随机化 (MR) 方法来研究身高、体重指数 (BMI)、腰臀比 (WHR)、臀围 (HC) 和腰围 (WC) 是否与骨质疏松症的两个主要特征——骨密度 (BMD) 和骨折——存在因果关系。从以前的大规模全基因组关联研究 (GWAS) 中获得与五个人体测量变量相关的全基因组显著 (p ≤ 5×10 ) 单核苷酸多态性 (SNP)，并将其用作工具变量。从大型英国生物库 GWAS 中获得估计的骨矿物质密度 (eBMD) 和骨折的汇总水平数据。在所使用的 MR 方法中，反向方差加权法是主要的分析方法，加权中位数、MR-Egger、基于模型的估计和 MR 多效性残差和异常值方法用于敏感性分析。本研究的结果表明，身高每增加一个标准差 (SD)，骨折风险增加 9.9%(比值比 [OR] = 1.099; 95%置信区间 [CI] 1.067-1.133;p = 8.793×10 )，估计的骨矿物质密度降低 0.080 SD(95%CI-0.106-(-0.054);p = 2.322×10 )。我们还发现 BMI 与 eBMD 存在因果关系 (β = 0.129, 95% CI 0.065-0.194;p = 8.113×10 )，但与骨折无关。经 BMI 调整的 WHR、经 BMI 调整的 HC 和经 BMI 调整的 WC 与骨折发生或 eBMD 无关。总之，本研究提供了遗传证据，证明人体测量学与骨矿物质密度或骨折风险之间存在某些因果关系。
