Abstract
PURPOSE: Statins may have a protective effect against osteoarthritis (including knee osteoarthritis and hip osteoarthritis); however, the link between statins and osteoarthritis risk is incompletely established. The aim of this study was to explore the relationship between statins and osteoarthritis risk through Mendelian randomization analysis using pooled information from a large population-wide genome-wide association study (GWAS). METHODS: Statin-related single-nucleotide polymorphisms (SNPs) were obtained from FinnGen's latest 9th edition database, and data on osteoarthritis, knee osteoarthritis, and hip osteoarthritis were acquired from the IEU OpenGWAS, the UK Biobank, and Arthritis Research UK Osteoarthritis Genetics (ArcOGEN) database, respectively. The inverse-variance weighting method is an important analysis method to estimate the causal effect. Weighted median method, simple median method, weighted median estimator method, and MR-Egger regression were employed to supplement the explanation. Odds ratio and 95%CI were used to evaluate the causal relationship among statins and the osteoarthritis risk, osteoarthritis in the knee, and osteoarthritis in the hip. Second, sensitivity analysis was carried out to validate the reliability of the results. Cochran's Q test was employed to test heterogeneity, MR-Egger intercept was employed to test whether horizontal pleiotropy existed, and single-nucleotide polymorphisms with potential influence were determined by the one-method analysis. RESULTS: (1) The results of the inverse variance weighting method showed Gene prediction indicated that statins were associated with osteoarthritis (OR = 0.998, 95% CI: 0.996-0.999, P = 0.01) and knee osteoarthritis (OR = 0.964, 95% CI: knee (0.940-0.989, P = 0.005) and hip osteoarthritis risk were associated (OR = 0.928, 95% CI: 0.901-0.955, P = 4.28 × 10(-7)). (2) MR-Egger intercept analysis did not detect potential horizontal pleiotropy (osteoarthritis: P = 0.658; knee osteoarthritis: P = 0.600; and hip osteoarthritis: P = 0.141). (3) The findings provide evidence that statins reduce osteoarthritis risk, osteoarthritis in the knee, and osteoarthritis in the hip, as described in observational studies, and the specific mechanisms by which statins treat osteoarthritis require further investigation. CONCLUSION: The results of this study, at the genetic level, reveal a negative causal relationship between statins and osteoarthritis, and this causal relationship is also present in knee and hip osteoarthritis. This study provides evidence against the potential of statins in the treatment of osteoarthritis, prompting the clinical treatment of osteoarthritis to consider improving the start and compliance of statins in the future.