Assessment of causal effects of physical activity on the risk of osteoarthritis: a two-sample Mendelian randomization study

Abstract

Abstract Background Growing evidence supports an association between physical activity (PA) and the risk of osteoarthritis (OA), but this may be influenced by confounding and reverse causality. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to reveal the causal relationship between PA and OA. Methods MR was performed to explore the causation of PA and OA with genetic variants as instrumental variables. The genetic variants were derived from the summary statistics of a large genome-wide association study meta-analysis based on the European population (n = 661,399), including self-reported leisure screen time (LST) and moderate-to-vigorous physical activity (MVPA), and Arthritis Research UK Osteoarthritis Genetics Consortium cohorts (417,596, 393,873 and 403,124 for overall, hip and knee OA, respectively). The major MR analysis used in this work was the inverse variance weighted (IVW) approach, and sensitivity, pleiotropy, and heterogeneity studies were performed to evaluate the validity of the findings. Results IVW estimates indicated that LST had a risk effect on overall OA (odds ratio (OR) = 1.309, 95% confidence interval (CI): 1.198–1.430, P = 2.330 × 10-9), hip OA (OR = 1.132, 95% CI: 1.009–1.269, P = 0.034) and knee OA (OR = 1.435. 95% CI: 1.286–1.602, P = 1.225 × 10-10). In contrast, no causal relationship was found between MVPA and OA (overall OA: OR = 0.895, 95% CI: 0.664–1.205, P = 0.465; hip OA: OR = 1.189, 95% CI: 0.792–1.786, P = 0.404; knee OA: OR = 0.707, 95% CI: 0.490 -1.021, P = 0.064). In addition, we observed significant heterogeneity in instrumental variables, but no horizontal pleiotropy was detected. Conclusions Recent findings demonstrated a protective impact of reducing LST on OA, independent of MVPA. This provides valuable insights into the role of physical activity in OA and offers lifestyle recommendations, such as reducing recreational sedentary behaviors and promoting appropriate exercise, for individuals at risk of OA.

Keywords

• Mendelian randomization
• Physical activity
• Osteoarthritis
• Causality