The Causal Effects of Lifestyle Factors on Osteoarthritis: A Two-sample Mendelian Randomisation Study

Modern sedentary lifestyles are prevalent among individuals with osteoarthritis. However, direct evidence linking such behaviours as causative factors of osteoarthritis remain limited due to the presence of confounding variables.

This study aims to determine the extent to which lifestyle factors have causal effects on osteoarthritis through a two-sample Mendelian randomisation (MR) study.

Exposure-outcome relationships were evaluated using inverse variance weighted twosample MR and summary statistics of genome-wide association studies of lifestyle factors and osteoarthritis. Weighted median, MR-PRESSO, and MR-Egger regression were used as sensitivity analyses. We obtained causality estimates, 95% confidence intervals (CI), and P-values from each MR method. Steiger filtering and radial filtering were used to exclude SNPs demonstrating reverse causality and significant heterogeneity, respectively.

MR analyses demonstrated that certain lifestyle factors had causal effects on osteoarthritis, particularly insomnia (OR 1.09 (0.387-1.79), P = 0.0024), BMI (OR 6.45 (4.48-8.42), P = 1.38e-10) and protein intake (OR 2.94 (0.361-5.52), P = 0.026). Effects were consistent across sensitivity analyses using median-based MR methods. ZNF131 & SEMA3F, and potentially RWDD2B & USP8 are genetic loci identified to mediate these causal effects.

Our results illustrate that lifetime exposure to certain lifestyle factors has causal effects on osteoarthritis. Further studies are required to determine the efficacy of lifestyle-based interventions in reducing the population-wide disease burden of osteoarthritis.