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

Area of Science:

• Genetics
• Epidemiology
• Orthopedics

Background:

• Osteoarthritis (OA) is a prevalent global joint disease with significant individual and societal impact.
• Observational studies suggest a link between walking pace (WP) and OA risk, but causality is unclear.
• Understanding the causal relationship is crucial for developing effective prevention strategies.

Purpose of the Study:

• To investigate the causal relationship between genetically predicted walking pace (WP) and the risk of osteoarthritis (OA).
• To examine the association of WP with overall OA, as well as its subtypes: knee OA and hip OA.
• To assess potential confounding factors influencing the WP-OA relationship.

Main Methods:

• A large-scale Mendelian randomization (MR) study utilizing European Genome-wide Association Study data.
• Employed single nucleotide polymorphisms (SNPs) associated with WP as instrumental variables.
• Utilized Inverse Variance Weighted (IVW) as the primary analysis, supported by MR-Egger, weighted median, and maximum likelihood methods.
• Performed sensitivity analyses for heterogeneity and pleiotropy, and multivariate MR (MVMR) for confounder adjustment.

Main Results:

• A genetically predicted increase in WP by one standard deviation was associated with a significant reduction in OA risk (OR=0.11).
• This association was consistent for knee OA (OR=0.17) and hip OA (OR=0.24).
• MVMR analysis confirmed the protective effect of WP against OA, independent of potential confounders.

Conclusions:

• This MR study establishes a significant causal link between faster walking pace and reduced susceptibility to osteoarthritis.
• Walking pace emerges as a potential prognostic factor for OA risk.
• Findings support the role of physical activity, specifically walking pace, in OA prevention.