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

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.