目的:肌肉减少症相关性状与缺血性卒中(IS)之间的因果关系尚不清楚。本研究旨在探讨肌少症相关性状对IS的因果影响,并确定这种关联的关键介质。
方法:我们进行了单变量,多变量双样本,和使用全基因组关联研究(GWAS)数据的两步孟德尔随机化(MR)分析。这包括阑尾瘦肉质量(ALM)的数据,手握力(HGS),和通常的步行速度(UWP)从英国生物银行,是来自MEGASTROKE联盟的数据。此外,根据其各自的GWAS数据集分析了21个候选介体。
结果:基因代理ALM的每1-SD增加与IS风险降低7.5%相关(95%CI:0.879-0.974),在控制体力活动水平和肥胖相关指数后,这种相关性仍然存在。两步MR鉴定出六种介体部分介导了较高ALM对IS的保护作用,最重要的是冠心病(CHD,中介比例:39.94%),其次是收缩压(36.51%),高血压(23.87%),舒张压(15.39%),2型糖尿病(T2DM,12.71%),低密度脂蛋白胆固醇(7.97%)。
结论:我们的研究揭示了高ALM对IS的因果保护作用,独立于体力活动和肥胖相关指数。此外,我们发现,较高的ALM可以通过降低血管危险因素的风险部分降低对IS的易感性,包括冠心病,高血压,T2DM,和高脂血症。简而言之,我们阐明了IS的另一个可改变的因素,并暗示维持足够的肌肉质量可能降低此类疾病的风险.
OBJECTIVE: The 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.
METHODS: We 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.
RESULTS: Each 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%).
CONCLUSIONS: Our 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.