Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
J Clin Endocrinol Metab. 2022 Mar 24;107(4):e1477-e1487. doi: 10.1210/clinem/dgab862.
Prolonged exposure to pathological cortisol, as in Cushing's syndrome causes various age-related disorders, including sarcopenia. However, it is unclear whether mild cortisol excess, for example, accelerates sarcopenia due to aging or chronic stress.
We used Mendelian randomization (MR) analysis to assess whether cortisol was causally associated with muscle strength and mass.
Three single-nucleotide polymorphisms associated with plasma cortisol concentrations in the CORtisol NETwork consortium (n = 12 597) were used as instrumental variables. Summary statistics with traits of interest were obtained from relevant genome-wide association studies. For the primary analysis, we used the fixed-effects inverse-variance weighted analysis accounting for genetic correlations between variants.
One SD increase in cortisol was associated with SD reduction in grip strength (estimate, -0.032; 95% CI -0.044 to -0.020; P = 3e-04), whole-body lean mass (estimate, -0.032; 95% CI, -0.046 to -0.017; P = 0.004), and appendicular lean mass (estimate, -0.031; 95% CI, -0.049 to -0.012; P = 0.001). The results were supported by the weighted-median analysis, with no evidence of pleiotropy in the MR-Egger analysis. The association of cortisol with grip strength and lean mass was observed in women but not in men. The association was attenuated after adjusting for fasting glucose in the multivariable MR analysis, which was the top mediator for the association in the MR Bayesian model averaging analysis.
This MR study provides evidence for the association of cortisol with reduced muscle strength and mass, suggesting the impact of cortisol on the development of sarcopenia.
长期暴露于病理性皮质醇（如库欣综合征）会导致各种与年龄相关的疾病，包括肌肉减少症。然而，皮质醇轻度增加是否会加速因衰老或慢性应激引起的肌肉减少症尚不清楚。
我们使用孟德尔随机化（MR）分析来评估皮质醇是否与肌肉力量和质量存在因果关系。
使用 CORtisol NETwork 联盟中与血浆皮质醇浓度相关的三个单核苷酸多态性（SNP）作为工具变量（instrumental variable）。从相关的全基因组关联研究中获得具有研究特征的汇总统计数据。在主要分析中，我们使用固定效应逆方差加权分析，同时考虑到变体之间的遗传相关性。
皮质醇增加 1 个标准差与握力降低 0.032 个标准差相关（估计值，-0.044 至 -0.020；P = 3e-04），全身瘦体重降低 0.032 个标准差（估计值，-0.046 至 -0.017；P = 0.004），四肢瘦体重降低 0.031 个标准差（估计值，-0.049 至 -0.012；P = 0.001）。加权中位数分析支持了这些结果，MR-Egger 分析未发现明显的异质性。皮质醇与握力和瘦体重的关联仅在女性中观察到，而在男性中未观察到。在多变量 MR 分析中，当调整空腹血糖后，这种关联减弱，而在 MR 贝叶斯模型平均分析中，空腹血糖是该关联的主要中介物。
这项 MR 研究为皮质醇与肌肉力量和质量下降之间的关联提供了证据，表明皮质醇对肌肉减少症的发展有影响。
