The causal roles of muscle weakness in cardiometabolic diseases and osteoporosis remain elusive. This two-sample Mendelian randomization (MR) study aims to explore the causal roles of muscle weakness in the risk of cardiometabolic diseases and osteoporosis. 15 single nucleotide polymorphisms (SNPs, P < 5 × 10⁻⁸) associated with muscle weakness were used as instrumental variables. Genetic predisposition to muscle weakness led to increased risk of coronary artery disease (inverse variance weighted [IVW] analysis, beta-estimate: 0.095, 95% confidence interval [CI]: 0.023 to 0.166, standard error [SE]:0.036, P-value = 0.009) and reduced risk of heart failure (weight median analysis, beta-estimate: − 0.137, 95% CI − 0.264 to − 0.009, SE:0.065, P-value = 0.036). In addition, muscle weakness may reduce the estimated bone mineral density (eBMD, weight median analysis, beta-estimate: − 0.059, 95% CI − 0.110 to − 0.008, SE:0.026, P-value = 0.023). We found no MR associations between muscle weakness and atrial fibrillation, type 2 diabetes or fracture. This study provides robust evidence that muscle weakness is causally associated with the incidence of coronary artery disease and heart failure, which may provide new insight to prevent and treat these two cardiometabolic diseases.

肌肉无力在心脏代谢疾病和骨质疏松症中的因果作用仍然难以捉摸。这项两个样本的孟德尔随机化 (MR) 研究旨在探讨肌肉无力与心脏代谢疾病和骨质疏松症风险之间的因果关系。与肌肉无力相关的15个单核苷酸多态性（SNP，P < 5 × 10 ^-8）被用作工具变量。肌肉无力的遗传倾向导致冠状动脉疾病的风险增加（逆方差加权 [IVW] 分析，β 估计值：0.095，95% 置信区间 [CI]：0.023 至 0.166，标准误差 [SE]：0.036，P-值 = 0.009）并降低心力衰竭风险（体重中值分析，β 估计值：− 0.137，95% CI − 0.264 至 − 0.009，SE：0.065，P 值 = 0.036）。此外，肌肉无力可能会降低估计的骨矿物质密度（eBMD，体重中值分析，β估计：− 0.059，95% CI − 0.110至− 0.008，SE：0.026，P值= 0.023）。我们发现肌肉无力与心房颤动、2 型糖尿病或骨折之间没有 MR 关联。这项研究提供了强有力的证据，表明肌肉无力与冠状动脉疾病和心力衰竭的发病率存在因果关系，这可能为预防和治疗这两种心脏代谢疾病提供新的见解。