Impact of Cortisol on Reduction in Muscle Strength and Mass: A Mendelian Randomization Study
Impact of Cortisol on Reduction in Muscle Strength and Mass: A Mendelian Randomization Study
复制标题
DOI：
10.1210/clinem/dgab862
复制
发表时间：
2021-12-21
影响因子：
5.8
通讯作者：
Ogawa, Yoshihiro
中科院分区：
文献类型：
--
作者：
Katsuhara, Shunsuke;Yokomoto-Umakoshi, Maki;Ogawa, Yoshihiro
背景长期暴露于病理性皮质醇（例如库欣综合征）会导致各种与年龄相关的疾病，包括肌肉减少症。然而，目前还不清楚轻微的皮质醇过量是否会加速由于衰老或慢性压力引起的肌肉减少症。目的采用孟德尔随机化分析法研究皮质醇与肌肉力量和质量的关系。方法以CORTISOL NETwork联合体（n = 12 597）中3个与血浆皮质醇浓度相关的单核苷酸多态性作为工具变量。从相关的全基因组关联研究中获得感兴趣性状的汇总统计量。对于主要分析，我们使用固定效应逆方差加权分析解释变异体之间的遗传相关性。结果皮质醇增加一个SD与握力减少一个SD相关（估计值，-0.032; 95% CI -0.044至-0.020; P = 3e-04），全身瘦体重（估计值，-0.032; 95%CI，-0.046至-0.017; P = 0.004）和非肥胖瘦体重（估计值，-0.031; 95%CI，-0.049至-0.012; P = 0.001）。结果得到了加权中位数分析的支持，在MR-Egger分析中没有多效性的证据。皮质醇与握力和瘦体重的关联在女性中观察到，但在男性中没有。在多变量MR分析中调整空腹血糖后，这种关联减弱，这是MR贝叶斯模型平均分析中关联的最大中介。结论本研究为皮质醇与肌肉力量和质量下降的相关性提供了证据，提示皮质醇在肌肉减少症的发生发展中的作用。
Context 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. Objective We used Mendelian randomization (MR) analysis to assess whether cortisol was causally associated with muscle strength and mass. Methods 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. Results 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. Conclusion 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.