Association of walking pace and risk of stroke: A two- sample mendelian randomization study in a European ancestry cohort

IF 2 4区医学 Q3 NEUROSCIENCES

Journal of Stroke & Cerebrovascular Diseases Pub Date : 2024-10-31 DOI:10.1016/j.jstrokecerebrovasdis.2024.108104

Cong Liang , Xinlin Huang , Yucui Pu , Pei Zhang , Rong Wang PhD

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引用次数: 0

Abstract

Background

Walking pace (WP), a simple physiological indicator, has been found to be strongly associated with a variety of health outcomes in recent years. Among them, the relationship between walking pace and stroke is of particular interest. Given the high morbidity, disability and mortality associated with stroke, identifying modifiable indicators of health, such as walking pace, could help in stroke prevention strategies. However, the causal relationship between WP and stroke risk remains unclear. This study aims to determine the causal relationship between walking pace and risk of stroke using a two-sample Mendelian randomization approach in a European-ancestry population.

Methods

In order to evaluate the potential for a causal relationship between WP and stroke in people of European heritage, a two-sample Mendelian randomization (MR) study was carried out. Statistics about the association of single nucleotide polymorphisms (SNPs) with stroke were taken from FinnGen (R8) (n = 284,040), while the UK Biobank genome-wide association studies (GWAS) provided the summary data on the association of SNPs with WP (n = 459,915). The inverse-variance weighted (IVW) method was utilised as the primary strategy to examine the causal connection between WP and stroke. Additionally, complementary analyses were conducted using the MR-Egger and weighted median. In order to identify the potential directional pleiotropy and heterogeneity, the MR-Egger intercept test, the MR-PRESSO test, and Cochran's Q statistic were all carried out. This connection was evaluated using OR with 95% confidence intervals (CIs).

Results

A total of 48 SNPs were identified as valid instrumental variables in our two-sample MR analysis. The result showed that a slower walking pace is associated with a higher risk of stroke (OR = 0.573; 95% CI, 0.383-0.858, P = 0.007). The “leave-one-out” analysis demonstrated that the absence of a single SNP did not affect the robustness of our results. The MR-Egger intercept test indicated that genetic pleiotropy did not introduce bias into the results [intercept = −2.9E−03, SE = 0.008, P = 0.719] and Cochran's Q test revealed no heterogeneity. Therefore, the sensitivity analyses yielded comparable results. Consequently, the results of the sensitivity analyses were consistent.

Conclusion

Our MR study revealed that WP is inversely associated with risk of stroke. These results provided evidence that slower WP causally increased the risk of stroke, recommending that patients with lower WP should have a prompt physical examination and targeted interventions to reduce their risk of stroke and enhance their quality of life.

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步行速度与中风风险的关系：欧洲血统队列中的双样本孟德尔随机研究

背景：步行速度（WP）作为一项简单的生理指标，近年来已被发现与多种健康结果密切相关。其中，步行速度与中风之间的关系尤其引人关注。鉴于中风的高发病率、高致残率和高死亡率，确定可改变的健康指标（如步行速度）有助于制定中风预防策略。然而，步行速度与中风风险之间的因果关系仍不清楚。本研究旨在采用双样本孟德尔随机方法，在欧洲籍人群中确定步行速度与中风风险之间的因果关系：为了评估欧洲血统人群中步行速度与中风之间的潜在因果关系，我们开展了一项双样本孟德尔随机化（MR）研究。单核苷酸多态性（SNPs）与中风相关性的统计数据来自芬兰基因组（FinnGen）（R8）（n = 284,040 个），而英国生物库（UK Biobank）全基因组关联研究（GWAS）提供了 SNPs 与 WP 相关性的汇总数据（n = 459,915 个）。反方差加权（IVW）法是研究 WP 与中风之间因果关系的主要策略。此外，还使用 MR-Egger 和加权中位数进行了补充分析。为了识别潜在的方向性多效性和异质性，还进行了 MR-Egger 截距检验、MR-PRESSO 检验和 Cochran's Q 统计量分析。结果显示，共发现了 48 个 SNPs：结果：在我们的双样本 MR 分析中，共有 48 个 SNPs 被确定为有效的工具变量。结果显示，步行速度越慢，中风风险越高（OR = 0.573；95% CI，0.383-0.858，P = 0.007）。剔除 "分析表明，单个 SNP 的缺失不会影响我们结果的稳健性。MR-Egger截距检验表明，遗传多效性没有给结果带来偏差[截距 = -2.9E-03，SE = 0.008，P = 0.719]，Cochran's Q 检验显示没有异质性。因此，敏感性分析得出的结果具有可比性。因此，敏感性分析的结果是一致的：我们的磁共振研究显示，WP 与中风风险成反比。这些结果提供了WP较低会增加中风风险的证据，建议WP较低的患者应及时进行体检并采取有针对性的干预措施，以降低中风风险并提高生活质量。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Stroke & Cerebrovascular Diseases Medicine-Surgery

CiteScore

5.00

自引率

4.00%

发文量

583

审稿时长

62 days

期刊介绍： The Journal of Stroke & Cerebrovascular Diseases publishes original papers on basic and clinical science related to the fields of stroke and cerebrovascular diseases. The Journal also features review articles, controversies, methods and technical notes, selected case reports and other original articles of special nature. Its editorial mission is to focus on prevention and repair of cerebrovascular disease. Clinical papers emphasize medical and surgical aspects of stroke, clinical trials and design, epidemiology, stroke care delivery systems and outcomes, imaging sciences and rehabilitation of stroke. The Journal will be of special interest to specialists involved in caring for patients with cerebrovascular disease, including neurologists, neurosurgeons and cardiologists.