Impact of Cortisol on Reduction in Muscle Strength and Mass: A Mendelian Randomization Study

Shunsuke Katsuhara, Maki Yokomoto-Umakoshi, Hironobu Umakoshi, Yayoi Matsuda, Norifusa Iwahashi, Hiroki Kaneko, Masatoshi Ogata, Tazuru Fukumoto, Eriko Terada, Ryuichi Sakamoto, Yoshihiro Ogawa

研究成果: ジャーナルへの寄稿学術誌査読

9 被引用数 (Scopus)


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.

ジャーナルJournal of Clinical Endocrinology and Metabolism
出版ステータス出版済み - 4月 1 2022

!!!All Science Journal Classification (ASJC) codes

  • 内分泌学、糖尿病および代謝内科学
  • 生化学
  • 内分泌学
  • 臨床生化学
  • 生化学、医学


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