The causal relationship between sarcopenia-related traits and ischemic stroke: Insights from univariable and multivariable Mendelian randomization analyses
AimsThe causal relationship between sarcopenia-related traits and ischemic stroke (IS) remains poorly understood. This study aimed to explore the causal impact of sarcopenia-related traits on IS and to identify key mediators of this association.MethodsWe conducted univariable, multivariable two-sample, and two-step Mendelian randomization (MR) analyses using genome-wide association study (GWAS) data. This included data for appendicular lean mass (ALM), hand grip strength (HGS), and usual walking pace (UWP) from the UK Biobank, and IS data from the MEGASTROKE consortium. Additionally, 21 candidate mediators were analyzed based on their respective GWAS data sets.ResultsEach 1-SD increase in genetically proxied ALM was associated with a 7.5% reduction in the risk of IS (95% CI: 0.879-0.974), and this correlation remained after controlling for levels of physical activity and adiposity-related indices. Two-step MR identified that six mediators partially mediated the protective effect of higher ALM on IS, with the most significant being coronary heart disease (CHD, mediating proportion: 39.94%), followed by systolic blood pressure (36.51%), hypertension (23.87%), diastolic blood pressure (15.39%), type-2 diabetes mellitus (T2DM, 12.71%), and low-density lipoprotein cholesterol (7.97%).ConclusionOur study revealed a causal protective effect of higher ALM on IS, independent of physical activity and adiposity-related indices. Moreover, we found that higher ALM could reduce susceptibility to IS partially by lowering the risk of vascular risk factors, including CHD, hypertension, T2DM, and hyperlipidemia. In brief, we elucidated another modifiable factor for IS and implied that maintaining sufficient muscle mass may reduce the risk of such disease. This study demonstrated that higher appendicular lean mass could reduce susceptibility to ischemic stroke, partially by lowering the risk of cardiovascular factors, such as coronary heart disease and hypertension. Preservation of muscle mass may potentially be a therapeutic intervention in stroke patients.image
基金：
National Natural Science Foundation ofChina, Grant/Award Number: 82101390and 82171297
第一作者机构：[1]Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing, Peoples R China[2]Beijing Inst Brain Disorders, Adv Ctr Stroke, Beijing, Peoples R China[3]Capital Med Univ, Xuanwu Hosp, Natl Ctr Neurol Disorders, Beijing 100053, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing, Peoples R China[2]Beijing Inst Brain Disorders, Adv Ctr Stroke, Beijing, Peoples R China[3]Capital Med Univ, Xuanwu Hosp, Natl Ctr Neurol Disorders, Beijing 100053, Peoples R China[*1]National Centerfor Neurological Disorders, XuanwuHospital, Capital Medical University,Beijing, 100053, China
推荐引用方式(GB/T 7714)：
Song Jiahao,Zhou Da,Li Jingrun,et al.The causal relationship between sarcopenia-related traits and ischemic stroke: Insights from univariable and multivariable Mendelian randomization analyses[J].CNS NEUROSCIENCE & THERAPEUTICS.2024,30(5):doi:10.1111/cns.14759.
APA：
Song, Jiahao,Zhou, Da,Li, Jingrun,Wang, Mengqi,Jia, Lina...&Meng, Ran.(2024).The causal relationship between sarcopenia-related traits and ischemic stroke: Insights from univariable and multivariable Mendelian randomization analyses.CNS NEUROSCIENCE & THERAPEUTICS,30,(5)
MLA：
Song, Jiahao,et al."The causal relationship between sarcopenia-related traits and ischemic stroke: Insights from univariable and multivariable Mendelian randomization analyses".CNS NEUROSCIENCE & THERAPEUTICS 30..5(2024)
