Causal effects of walking pace on osteoarthritis: a two-sample mendelian randomization study

Peng Qiu; Junyu Wu; Lihong Kui; Mingxian Chen; Shuaibing Lv; Zhongkai Zhang

doi:10.3389/fgene.2023.1266158

Causal effects of walking pace on osteoarthritis: a two-sample mendelian randomization study

Front Genet. 2023 Oct 11:14:1266158. doi: 10.3389/fgene.2023.1266158. eCollection 2023.

Authors

Peng Qiu¹, Junyu Wu², Lihong Kui³, Mingxian Chen⁴, Shuaibing Lv², Zhongkai Zhang¹

Affiliations

¹ Department of Rehabilitation, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
² School of Physical Education, Shanghai University of Sport, Shanghai, China.
³ Xiamen Rehabilitation Hospital, Xiamen, China.
⁴ School of Exercise and Health, Shanghai University of Sport, Shanghai, China.

Abstract

Background: Osteoarthritis (OA) is one of the most common joint diseases worldwide, imposing a substantial burden on individuals and society. Numerous pieces of evidence suggest that walking pace (WP) can serve as a predictive indicator for the risk of various diseases, and observational studies have also found a potential link between WP and the risk of OA. However, the causal relationship between WP and the risk of OA remains unclear. Methods: We conducted a mendelian randomization (MR) study using data from the European Genome-wide Association Study, which included WP (including 459,915 participants), OA (including 10,083 cases and 40,425 controls), knee OA (including 24,955 cases and 378,169 controls), and hip OA (including 15,704 cases and 378,169 controls). Single nucleotide polymorphisms (SNPs) associated with WP were utilized to infer causal associations with OA and its subtypes. The Inverse Variance Weighted (IVW) technique served as the primary causal analysis method. Three auxiliary MR methods - MR-Egger, weighted median, and maximum likelihood - were used to substantiate the IVW results. Sensitivity analyses were performed to examine heterogeneity and pleiotropy. In addition, multivariate MR (MVMR) analysis was used to assess causality after adjustment for three potential confounders. Results: According to the results of the IVW method, every 1 standard deviation increased in genetic WP corresponds to an 89% reduction in the risk of OA (odds ratio (OR) = 0.11; 95% confidence interval (CI), 0. 06-0.19; p = 1.57 × 10^-13), an 83% reduction in the risk of knee OA (OR = 0.17; 95% CI, 0.11-0.28; p = 2.78 × 10^-13), and a 76% reduction in the risk of hip OA (OR = 0.24; 95% CI, 0.14-0.43; p = 1.51 × 10^-6). These results were confirmed by the three additional MR methods and validated by the sensitivity analysis. Ultimately, the MVMR analysis confirmed that the role of WP in reducing the risk of OA and its subtypes remains consistent regardless of potential confounders. Conclusion: The results of our MR study highlight a significant causal association between WP and the susceptibility to OA, including its knee and hip subtypes. These findings propose that WP could be utilized as a potential prognostic factor for OA risk.

Keywords: causal relationship; genome-wide association studies; mendelian randomization; osteoarthritis; walking pace.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was funded by Wenzhou Municipal Science and Technology Plan Project (Grant No. Y2020534).