自我报告的步行速度与心血管疾病风险：一项两样本孟德尔随机化研究。
Self-Reported Walking Pace and Risk of Cardiovascular Diseases: A Two-Sample Mendelian Randomization Study.
作者信息
Chen Lu, Sun Xingang, He Yuxian, Zheng Liangrong
机构信息
Department of Cardiology and Atrial Fibrillation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
出版信息
Front Genet. 2022 Jun 16;13:871302. doi: 10.3389/fgene.2022.871302. eCollection 2022.
In observational studies, the self-reported walking pace has been associated with the risk of cardiovascular diseases (CVD). However, whether those associations indicate causal links remains unclear. We performed two-sample Mendelian randomization (MR) analyses to evaluate the causal effect of walking pace on several CVD outcomes, including atrial fibrillation (AF), heart failure (HF), any stroke, ischemic stroke (IS), and IS subtypes. Genetic variants associated with self-reported walking pace were selected as instrumental variables (IVs) from the latest genome-wide association studies (GWAS). Summary-level data for outcomes were obtained from the corresponding GWAS and the FinnGen consortium. The random-effects inverse variance weighted (IVW) method was used as the main MR analysis, supplemented by replication analyses using data from the FinnGen. To explore the effect of pleiotropy due to adiposity-related traits, we further conducted MR analyses by excluding the adiposity-related IVs and regression-based multivariable MR adjusting for body mass index (BMI). The MR results indicated significant inverse associations of self-reported walking pace with risks of AF [odds ratio (OR), 0.577; 95% confidence interval (CI), 0.442, 0.755; = 5.87 × 10], HF (OR, 0.307; 95% CI, 0.229, 0.413; = 5.31 × 10), any stroke (OR, 0.540; 95% CI, 0.388, 0.752; = 2.63 × 10) and IS (OR, 0.604; 95% CI, 0.427, 0.853; = 0.004) and suggestive inverse association of self-reported walking pace with cardioembolic stroke (CES) (OR, 0.492; 95% CI, 0.259, 0.934; = 0.030). Similar results were replicated in the FinnGen consortium and persisted in the meta-analysis. However, there was no causality between walking pace and large artery stroke (OR, 0.676; 95% CI, 0.319, 1.434; = 0.308) or small vessel stroke (OR, 0.603; 95% CI, 0.270, 1.349; = 0.218). When excluding adiposity-related IVs and adjusting for BMI, the associations for HF and any stroke did not change substantially, whereas the associations for AF, IS, and CES were weakened. Our findings suggested that genetically predicted increasing walking pace exerted beneficial effects on AF, HF, any stroke, IS, and CES. Adiposity might partially mediate the effect of walking pace on AF, IS, and CES.
在观察性研究中，自我报告的步行速度与心血管疾病（CVD）风险相关。然而，这些关联是否表明因果关系仍不清楚。我们进行了两样本孟德尔随机化（MR）分析，以评估步行速度对几种CVD结局的因果效应，包括心房颤动（AF）、心力衰竭（HF）、任何中风、缺血性中风（IS）以及IS亚型。从最新的全基因组关联研究（GWAS）中选择与自我报告的步行速度相关的基因变异作为工具变量（IVs）。结局的汇总水平数据来自相应的GWAS和芬兰基因联盟。随机效应逆方差加权（IVW）方法用作主要的MR分析，并辅以使用芬兰基因联盟数据的重复分析。为了探讨与肥胖相关性状的多效性影响，我们通过排除与肥胖相关的IVs并基于回归的多变量MR调整体重指数（BMI），进一步进行了MR分析。MR结果表明，自我报告的步行速度与AF风险呈显著负相关[比值比（OR），0.577；95%置信区间（CI），0.442，0.755；P = 5.87×10⁻³]、HF（OR，0.307；95%CI，0.229，0.413；P = 5.31×10⁻⁶）、任何中风（OR，0.540；95%CI，0.388，0.752；P = 2.63×10⁻³）和IS（OR，0.604；95%CI，0.427，0.853；P = 0.004），并且自我报告的步行速度与心源性栓塞性中风（CES）呈提示性负相关（OR，0.492；95%CI，0.259，0.934；P = 0.030）。类似结果在芬兰基因联盟中得到重复，并在荟萃分析中持续存在。然而，步行速度与大动脉中风（OR，0.676；95%CI，0.319，1.434；P = 0.308）或小血管中风（OR，0.603；95%CI，0.270，1.349；P = 0.218）之间不存在因果关系。当排除与肥胖相关的IVs并调整BMI时，HF和任何中风的关联没有实质性变化，而AF、IS和CES的关联则被削弱。我们的研究结果表明，基因预测的步行速度增加对AF、HF、任何中风、IS和CES具有有益影响。肥胖可能部分介导了步行速度对AF、IS和CES的影响。
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