Genetically predicted sex hormone-binding globulin and bone mineral density:​ a Mendelian randomization study

Qu, Zihao<sup>1,2</sup>; Jiang, Jiuzhou<sup>3</sup>; Yang, Fangkun<sup>4</sup>; Huang, Jiawei<sup>5</sup>; Zhao, Jianqiang<sup>6</sup>; Yan, Shigui<sup>1,2</sup>

Affiliations

¹Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China

²Orthopedic Research Institute of Zhejiang University, Hangzhou 310009, Zhejiang, China

³Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, China

⁴Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China

⁵Spine Lab, Department of Orthopedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

⁶Department of Cardiology and Atrial Fibrillation Center, The First Affiliated Hospital of Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang, China

Abstract and keywords

Previous observational studies have identified various risk factors associated with the development of osteoporosis, including sex hormone-binding globulin (SHBG). The aim of this study was to determine the potential causal effects of circulating SHBG concentrations on bone mineral density (BMD). Two-sample Mendelian randomization (MR) approach was applied in analyses. From summary-level data of genome-wide association studies (GWAS), we selected 11 single-nucleotide polymorphisms (SNPs) associated with SHBG levels as instrumental variable, and used summary statistics for BMD at forearm (FA) (n = 8143), femoral neck (FN) (n = 32,735), lumbar spine (LS) (n = 28,498) and heel (HL) (n = 394,929), and total-body BMD of different age-stages (15 or less, 15–30, 30–45, 45–60, 60 or more years old) (n = 67,358). Inverse causal associations was observed between SHBG levels and FA BMD (Effect = − 0.26; 95% CI − 0.49 to − 0.04; P = 0.022), HL eBMD (Effect = − 0.09; 95% CI − 0.12 to − 0.06; P = 3.19 × 10^–9), and total-body BMD in people aged 45–60 years (Effect = − 0.16; 95% CI − 0.31 to − 2.4 × 10^–3; P = 0.047) and over 60 years (Effect = − 0.19; 95% CI − 0.33 to − 0.05; P = 0.006). Our study demonstrates that circulating SHBG concentrations are inversely associated with FA and HL eBMD, and total-body BMD in people aged over 45 years, suggesting that the role of SHBG in the development of osteoporosis might be affected by chronological age of patients and skeletal sites.

Keywords: Sex hormone-binding globulin; Bone mineral density; Osteoporosis; Mendelian randomization; Causal effect

Links

DOI: 10.1007/s00223-020-00770-8

PubMed: 33068140

WoS: 000579443100002

History

Received: 2020-05-21

Accepted: 2020-10-07

Online: 2020-10-17

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Cited By (1)

Year	Entry
2023	Qu Y, Xiao C, Wu X, Zhu J, Qin C, He L, Cui H, Zhang L, Zhang W, Yang C, Yao Y, Li J, Liu Z, Zhang B, Wang W, Jiang X. Genetic correlation, shared loci, and causal association between sex hormone-binding globulin and bone mineral density: insights from a large-scale genomewide cross-trait analysis. J Bone Miner Res. November 2023;38(11):1635-1644.