Lv Yan, Du Yong-Jun, Liu Jia-Mian, Liao Jian-Qing, Ma Cheng-Jie, Xu Rui, Fang Jun-Hua, Zhao Lv, Pu Shao-Quan, Lu Sheng
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650504, Yunnan, China.
Department of Orthopedics, The First People's Hospital of Yunnan Province, Kunming, 650032, Yunnan, China.
J Bone Miner Metab. 2025 Jun 6. doi: 10.1007/s00774-025-01612-z.
Sarcopenia is closely related to osteoporosis, but the causal direction of these associations remains unclear. This study aims to explore these potential causal associations from the perspective of gene regulation.
Differentially expressed genes between sarcopenia and control, were identified as exposure factors, with osteoporosis serving as outcome variable, to identify key genes that had potential causal association with osteoporosis. Further analysis was conducted to investigate the causal links between key genes and sarcopenia-related characteristics. Moreover, enrichment analyses, ceRNA and Gene-Gene Interaction network were studied.
Only SCD1 demonstrated a potential causal association with osteoporosis (OR = 0.9970, P = 0.0217), acting as a protective factor against the disease. The potential causal links between SCD1 and sarcopenia-related characteristics are executed. SCD1 was identified as a risk factor for low hand grip strength (OR = 1.1397, P = 0.0290), while being pinpointed as a protective factor for appendicular lean mass (OR = 0.8777, P = 0.0147), usual walking pace (OR = 0.9834, P = 0.0290), whole body fat-free mass (OR = 0.9412, P = 0.0227), and trunk fat-free mass (OR = 0.9425, P = 0.0257). All analyses passed Steiger directional test, indicating a unidirectional causal association. Moreover, indicated that SCD1 was significantly associated with metabolic pathways related to lipid biosynthesis and regulation.
SCD1 was identified as a protective factor for osteoporosis and a risk factor for sarcopenia. This research provides new insights for the study of sarcopenia and osteoporosis, and offers theoretical backing for the positive effects of exercise in the elderly.
肌肉减少症与骨质疏松症密切相关，但这些关联的因果方向仍不明确。本研究旨在从基因调控的角度探索这些潜在的因果关联。
将肌肉减少症与对照组之间的差异表达基因确定为暴露因素，以骨质疏松症作为结果变量，识别与骨质疏松症有潜在因果关联的关键基因。进一步分析以研究关键基因与肌肉减少症相关特征之间的因果联系。此外，还进行了富集分析、ceRNA和基因-基因相互作用网络研究。
只有硬脂酰辅酶A去饱和酶1（SCD1）显示出与骨质疏松症有潜在的因果关联（比值比[OR]=0.9970，P=0.0217），是预防该疾病的保护因素。SCD1与肌肉减少症相关特征之间的潜在因果联系得以确定。SCD1被确定为低握力的危险因素（OR=1.1397，P=0.0290），而被确定为四肢瘦体重的保护因素（OR=0.8777，P=0.0147）、平常步行速度的保护因素（OR=0.9834，P=0.0290）、全身无脂肪质量的保护因素（OR=0.9412，P=0.0227）以及躯干无脂肪质量的保护因素（OR=0.9425，P=0.0257）。所有分析均通过斯泰格方向性检验，表明存在单向因果关联。此外，表明SCD1与脂质生物合成和调控相关的代谢途径显著相关。
SCD1被确定为骨质疏松症的保护因素和肌肉减少症的危险因素。本研究为肌肉减少症和骨质疏松症的研究提供了新的见解，并为运动对老年人的积极影响提供了理论支持。
