Sha Tingting, Zhang Yuqing, Joshi Amit D, Lane Nancy E, Wei Jie, Li Wei, Xie Haibin, Li Jinchen, Li Changjun, Zeng Chao, Lei Guanghua, Wang Yilun
Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China.
Hunan Key Laboratory of Joint Degeneration and Injury, Changsha, China.
BMJ Open. 2025 Apr 7;15(4):e091656. doi: 10.1136/bmjopen-2024-091656.
Observational studies have found that cigarette smoking increased the prevalence and incidence of sarcopenia, whereas alcohol consumption appeared to decrease the risk. These findings, however, may be susceptible to either confounding bias or reverse causation. We conducted a Mendelian randomisation (MR) study to appraise the causal relation of cigarette smoking and alcohol consumption to the risk of sarcopenia.
Genetic instruments associated with cigarette smoking (cigarettes per day) and alcohol consumption (drinks per week) were retrieved from the publicly available genome-wide association data. Individual-level, electronic medical record-linked data on sarcopenia, grip strength and appendicular lean mass were obtained from the UK Biobank. We performed two-sample univariable and multivariable MR analyses to examine the relation of genetically determined cigarette smoking and alcohol consumption to the risk of sarcopenia and its indices.
One SD increase of genetically determined cigarette smoking was associated with an increased risk of sarcopenia (OR=2.51, 95% CI: 1.26 to 5.01, p=0.001), decreased grip strength (β=-0.63 kg, 95% CI: -1.13 to -0.13, p=0.01) and less appendicular lean mass (β=-0.22 kg, 95% CI: -0.44 to -0.01, p=0.04). Although one SD increase of genetically determined alcohol consumption was associated with decreased grip strength (β=-1.15 kg, 95% CI: -2.09 to -0.10, p=0.02), no statistically significant causal association was observed between genetically determined alcohol consumption and either sarcopenia (OR=0.96, 95% CI: 0.35 to 2.62, p=0.94) or appendicular lean mass (β=-0.23 kg, 95% CI: -0.91 to 0.45, p=0.51).
Our findings showed that genetically determined cigarette smoking, but not alcohol consumption, was causally associated with the risk of sarcopenia.
观察性研究发现，吸烟会增加肌肉减少症的患病率和发病率，而饮酒似乎会降低患病风险。然而，这些发现可能容易受到混杂偏倚或反向因果关系的影响。我们进行了一项孟德尔随机化（MR）研究，以评估吸烟和饮酒与肌肉减少症风险之间的因果关系。
从公开的全基因组关联数据中检索与吸烟（每日吸烟量）和饮酒（每周饮酒量）相关的遗传工具。关于肌肉减少症、握力和四肢瘦体重的个体水平电子病历关联数据来自英国生物银行。我们进行了两样本单变量和多变量MR分析，以研究基因决定的吸烟和饮酒与肌肉减少症风险及其指标之间的关系。
基因决定的吸烟量每增加一个标准差，肌肉减少症风险增加（OR=2.51，95%CI：1.26至5.01，p=0.001），握力降低（β=-0.63kg，95%CI：-1.13至-0.13，p=0.01），四肢瘦体重减少（β=-0.22kg，95%CI：-0.44至-0.01，p=0.04）。虽然基因决定的饮酒量每增加一个标准差与握力降低有关（β=-1.15kg，95%CI：-2.09至-0.10，p=0.02），但在基因决定的饮酒量与肌肉减少症（OR=0.96，95%CI：0.35至2.62，p=0.94）或四肢瘦体重（β=-0.23kg，95%CI：-0.91至0.45，p=0.51）之间未观察到统计学上显著的因果关联。
我们的研究结果表明，基因决定的吸烟而非饮酒与肌肉减少症风险存在因果关联。
