Genetic causal relationship between physical activity and osteoarthritis: a two-sample Mendelian randomization study.

Area of Science:

• Genetics
• Orthopedics
• Epidemiology

Background:

• Physical activity (PA) plays a complex role in osteoarthritis (OA), potentially preventing or exacerbating it.
• The genetic basis for the relationship between PA and OA remains largely unexplored.
• Understanding this genetic link is crucial for developing targeted OA prevention and treatment strategies.

Purpose of the Study:

• To investigate the potential genetic causal relationship between different types of physical activity and knee osteoarthritis (KOA).
• To identify shared genetic factors that may link physical activity levels to KOA susceptibility.
• To clarify the role of genetics in the association between physical activity and OA.

Main Methods:

• Utilized genome-wide association study (GWAS) summary data for three physical activity types: moderate to vigorous physical activity (MVPA), vigorous physical activity (VPA), and strenuous sports or other exercises (SSOE).
• Employed a two-sample Mendelian randomization (MR) analysis with sensitivity analyses, including MR-Egger, MR-PRESSO, and MR-RAPS, to assess heterogeneity and pleiotropy.
• Performed leave-one-out analyses to ensure robustness of the findings against individual genetic variants.

Main Results:

• No significant genetic causal relationship was found between MVPA, VPA, or SSOE and knee osteoarthritis (KOA).
• Statistical analyses revealed no significant heterogeneity or horizontal pleiotropy, indicating reliable MR estimates.
• Sensitivity analyses confirmed that the results were not driven by single nucleotide polymorphisms (SNPs) and were normally distributed.

Conclusions:

• This study provides evidence against a direct genetic causal link between physical activity levels and knee osteoarthritis.
• The findings suggest that any observed association between physical activity and KOA may be mediated through non-genetic pathways.
• Further investigation into non-genetic mechanisms is warranted to fully understand the complex interplay between physical activity and osteoarthritis.