Introduction:
Appropriate levels of physical activity (PA) can help prevent osteoarthritis (OA) and alleviate its symptoms. This study aims to clarify the causal link between PA and OA by investigating their shared genetic factors.

Material and methods:
The study utilized genome-wide association analysis (GWAS) summary data to investigate the relationship between three types of PA, include moderate to vigorous physical activity (MVPA), vigorous physical activity (VPA) and strenuous sports or other exercises (SSOE), and knee osteoarthritis (KOA). A two-sample Mendelian randomization (MR) study was conducted using the TwoSampleMR and MRPRESSO packages in R. We did a sensitivity analysis, including heterogeneity, horizontal pleiotropy, outliers, and assessed for influence by a single single-nucleotide polymorphisms (SNPs) and for compliance with normal distribution.

Results:
The results of the MR analysis indicate that MVPA (P = 0.436, OR 95% CI = 1.814 [0.405-8.119]), VPA (P = 0.995, OR 95% CI = 1.011 [0.040-25.224]) and SSOE (P = 0.266, OR 95% CI = 0.258 [0.024-2.812]) have no significant genetic causal relationship with KOA. We did not detect any heterogeneity or horizontal pleiotropy (P > 0.05), nor were there any outliers in our MR analysis. Our MR results were not driven by a single SNP and were normally distributed (P > 0.05).

Conclusions:
The results of this study provide evidence that there is no genetic causal relationship between PA and KOA, thereby contributing to the understanding of their correlation. However, it cannot be excluded that a relationship may exist between the two at other levels beyond the scope of genetic factors.