Causal Associations of Anthropometric Measurements With Fracture Risk and Bone Mineral Density: A Mendelian Randomization Study

作者：Baoshan Ma, Chongyang Li, Jianqiao Pan, Shuzheng Zhang, Heng Dong, Yiming Wu, Jun Lv · 发表于：Journal of Bone and Mineral Research · 年份：2020 · DOI：10.1002/jbmr.4296 · 被引用次数：28 · 研究领域：Genetic Associations and Epidemiology、Liver Disease Diagnosis and Treatment、Growth Hormone and Insulin-like Growth Factors

ABSTRACT 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 × 10−8) 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...