Department of Orthopedics, The First Hospital of Changsha, Changsha, China.
Department of Orthopedics, Peking University Third Hospital, Beijing, China.
Front Public Health. 2024 Oct 23;12:1415343. doi: 10.3389/fpubh.2024.1415343. eCollection 2024.
Previous observational studies have suggested associations between high-level educational attainment (EA) and a lower risk of sarcopenia. However, the causality inferred from those studies was subjected to residual confounding and reverse causation. The protective effect of EA on sarcopenia may be mediated via changes in brain cortical structure. The aim of this study was to use a two-step Mendelian randomization (MR) analysis to illustrate the causal relationship between EA, brain cortical structure, and sarcopenia.
Instrumental variables at the genome-wide significance level were obtained from publicly available datasets, and inverse variance weighted as the primary method was used for MR analysis. We perform several sensitivity analyses, including Cochran Q test, MR-Egger intercept test, leave-one-out analyses, and MR Pleiotropy Residual Sum and Outlier to evaluate the reliability of the results.
EA was causally associated with increased appendicular lean mass ( = 0.25, 95% confidence interval (CI): 0.19 to 0.31, = 2.25 × 10), hand grip strength (left: = 0.042, 95% CI: 0.013 to 0.071, = 4.77 × 10 and right: = 0.050, 95% CI: 0.022 to 0.079, = 5.17 × 10), and usual walking pace (β = 0.20, 95% CI: 0.18 to 0.22, = 6.16 × 10). In addition, EA was associated with increased brain cortical surface area ( = 4082.36, 95% CI: 2513.35 to 5681.38, = 3.40 × 10) and cortical thickness (TH) ( = 0.014, 95% CI: 0.0045 to 0.023, = 3.45 × 10). Regarding the causal effect of EA on usual walking pace, the mediatory effect of TH was 0.0069 and the proportion of mediation by TH was 3.43%.
The study will have revealed the protective causal effect of EA on sarcopenia, which provides a reference for the prevention of sarcopenia at the public health level. We also will have found EA could affect the brain cortical structure, and the brain cortical structure could mediate the protective effect of EA against sarcopenia risk.
先前的观察性研究表明，高水平的教育程度（EA）与较低的肌肉减少症风险之间存在关联。然而，这些研究中推断的因果关系受到残余混杂和反向因果关系的影响。EA 对肌肉减少症的保护作用可能通过大脑皮质结构的变化来介导。本研究旨在使用两步孟德尔随机化（MR）分析来阐明 EA、大脑皮质结构和肌肉减少症之间的因果关系。
从公开可用的数据集获得全基因组显著水平的工具变量，并使用逆方差加权作为主要方法进行 MR 分析。我们进行了几项敏感性分析，包括 Cochran Q 检验、MR-Egger 截距检验、单样本分析和 MR 偏倚残差和异常值分析，以评估结果的可靠性。
EA 与增加四肢瘦体重（ = 0.25，95%置信区间（CI）：0.19 至 0.31， = 2.25 × 10）、握力（左手： = 0.042，95%CI：0.013 至 0.071， = 4.77 × 10，右手： = 0.050，95%CI：0.022 至 0.079， = 5.17 × 10）和通常的步行速度（β = 0.20，95%CI：0.18 至 0.22， = 6.16 × 10）之间存在因果关系。此外，EA 与大脑皮质表面积增加（ = 4082.36，95%CI：2513.35 至 5681.38， = 3.40 × 10）和皮质厚度（TH）（ = 0.014，95%CI：0.0045 至 0.023， = 3.45 × 10）有关。关于 EA 对通常步行速度的因果效应，TH 的中介效应为 0.0069，TH 的中介效应比例为 3.43%。
该研究将揭示 EA 对肌肉减少症的保护因果效应，为公共卫生水平预防肌肉减少症提供参考。我们还发现 EA 可以影响大脑皮质结构，而大脑皮质结构可以介导 EA 对肌肉减少症风险的保护作用。
