OP0146 GENETIC EVIDENCE REVEALS A CAUSAL RELATIONSHIP BETWEEN PHYSICAL ACTIVITY AND OSTEOARTHRITIS

Abstract

Background: Osteoarthritis (OA) is a common musculoskeletal disease [1]. Research evidence indicates that exercise can reduce OA patients' joint pain to an extent [2]. However, the genetic causal relationship between physical activity (PA) and OA remains vague. Objectives: In our study, Mendelian randomization (MR) was conducted to explore the causal assosiation of PA and OA. Methods: PA was divided into two different phenotypes, including sedentary behavior and physically active behavior. Genome-wide association study (GWAS) data for PA [3] was obtained from the UK Biobank. We selected single nucleotide polymorphisms (SNPs) that were strongly associated (p < 5 × 10-8) with two PA phenotypes and checked them on PhenoScanner removing SNPs associated with confounders. The OA data was derived from a GWAS among 455,221 individuals (77052 samples and 378169 controls) of European descent [4]. To assess the causality of PA on OA, inverse variance weighting (IVW), MR-Egger, and weighted median (WM), were employed. IVW was applied for the principal analysis. To ensure the robustness of our result, Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis were used to assess the sensitivity of the study. Results: Among the tested sedentary behavior, the length of mobile phone use increases the risk of knee OA (odds ratio (OR):1.560, 95% confidence interval (CI):1.167-2.086, p=2.683×10-3) and hip or knee OA (OR:1.334, 95%CI:1.026-1.734, p=3.141×10-2). After removing SNPs associated with smoking, alcohol consumption, lymphocyte count, and heart disease, we also found evidence of a potential adverse effect of genetically predicted time spent watching television (TV) on knee OA (OR:1.913, CI:1.450-2.523, p=4.388×10-6) and hip or knee OA (OR:1.611, 95%CI:1.288-2.014, p=2.860×10-5). No potential causal link was observed between physically active behavior and OA through the IVW analysis( p>0.05). MR-Egger and WM yielded identical effects to IVW. Any potential heterogeneity or pleiotropy was not found. Conclusion: Sedentary behavior can increase the risk of OA, but no direct causal relationship is observed between physically active behavior and OA. It indicates that OA patients should avoid a sedentary lifestyle.