Research Paper Volume 14, Issue 14 pp 5681—5698
A bi-directional Mendelian randomization study of the sarcopenia-related traits and osteoporosis
- 1 Center for System Biology, Data Sciences, and Reproductive Health, School of Basic Medical Science, Central South University, Changsha, Hunan Province, P.R. China
- 2 Tulane Center of Biomedical Informatics and Genomics, Deming Department of Medicine, School of Medicine, Tulane University, New Orleans, LA 70112, USA
Received: February 3, 2022 Accepted: June 20, 2022 Published: July 2, 2022https://doi.org/10.18632/aging.204145
How to Cite
Copyright: © 2022 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Both sarcopenia and osteoporosis are common geriatric diseases causing huge socioeconomic burdens, and clinically, they often occur simultaneously. Observational studies have found a controversial correlation between sarcopenia and osteoporosis and their causal relationship is not clear. Therefore, we performed a bi-directional two-sample Mendelian randomization (MR) analysis to assess the potential causal relationship between sarcopenia-related traits (hand grip strength, lean mass, walking pace) and osteoporosis. Our analysis was performed by applying genetic variants obtained from the UK Biobank and the GEnetic Factors for OSteoporosis (GEFOS) datasets. We used inverse-variance weighted (IVW) and several sensitivity analyses to estimate and cross-validate the potential causal relationship in this study. We found that bone mineral density (BMD) was causally positively associated with left-hand grip strength (β = 0.017, p-value = 0.001), fat-free mass (FFM; right leg FFM, β = 0.014, p-value = 0.003; left arm FFM, β = 0.014, p-value = 0.005), but not walking pace. Higher hand grip strength was potentially causally associated with increased LS-BMD (right-hand grip strength, β = 0.318, p-value = 0.001; left-hand grip strength, β = 0.358, p-value = 3.97 × 10–4). In conclusion, osteoporosis may be a risk factor for sarcopenia-related traits and muscle strength may have a site-specific effect on BMD.
pQCT: peripheral quantitative computed tomography; MR: Mendelian randomization; IVs: instrumental variables; GWASs: genome-wide association studies; BMD: bone mineral density; LD: linkage disequilibrium; FFM: fat-free mass; IVW: inverse-variance weighted; MR-PRESSO: Mendelian Randomization Pleiotropy RESidual Sum and Outlier; RAPS: Robust Adjusted Profile Score; SNPs: single nucleotide polymorphisms; LS-BMD: lumbar spine BMD; FNK-BMD: femoral neck BMD; CI: confidence interval; ALM: appendicular lean mass; DXA: Dual energy X-ray absorptiometry; BIA: bioelectrical impedance analysis; QUS: quantitative ultrasound; eBMD: estimated BMD; GEFOS: the GEnetic Factors for Osteoporosis; WBLM: whole-body lean mass.