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

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 hav...

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Autores principales: Qiu, Peng, Wu, Junyu, Kui, Lihong, Chen, Mingxian, Lv, Shuaibing, Zhang, Zhongkai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10598773/
https://www.ncbi.nlm.nih.gov/pubmed/37886687
http://dx.doi.org/10.3389/fgene.2023.1266158
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author Qiu, Peng
Wu, Junyu
Kui, Lihong
Chen, Mingxian
Lv, Shuaibing
Zhang, Zhongkai
author_facet Qiu, Peng
Wu, Junyu
Kui, Lihong
Chen, Mingxian
Lv, Shuaibing
Zhang, Zhongkai
author_sort Qiu, Peng
collection PubMed
description 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.
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spelling pubmed-105987732023-10-26 Causal effects of walking pace on osteoarthritis: a two-sample mendelian randomization study Qiu, Peng Wu, Junyu Kui, Lihong Chen, Mingxian Lv, Shuaibing Zhang, Zhongkai Front Genet Genetics 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. Frontiers Media S.A. 2023-10-11 /pmc/articles/PMC10598773/ /pubmed/37886687 http://dx.doi.org/10.3389/fgene.2023.1266158 Text en Copyright © 2023 Qiu, Wu, Kui, Chen, Lv and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Qiu, Peng
Wu, Junyu
Kui, Lihong
Chen, Mingxian
Lv, Shuaibing
Zhang, Zhongkai
Causal effects of walking pace on osteoarthritis: a two-sample mendelian randomization study
title Causal effects of walking pace on osteoarthritis: a two-sample mendelian randomization study
title_full Causal effects of walking pace on osteoarthritis: a two-sample mendelian randomization study
title_fullStr Causal effects of walking pace on osteoarthritis: a two-sample mendelian randomization study
title_full_unstemmed Causal effects of walking pace on osteoarthritis: a two-sample mendelian randomization study
title_short Causal effects of walking pace on osteoarthritis: a two-sample mendelian randomization study
title_sort causal effects of walking pace on osteoarthritis: a two-sample mendelian randomization study
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10598773/
https://www.ncbi.nlm.nih.gov/pubmed/37886687
http://dx.doi.org/10.3389/fgene.2023.1266158
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