Two-sample Mendelian randomization analysis of the relationship between statins and the risk of osteoarthritis
Wu Ruiqi1, Zhang Xuan1, Zhou Yi1, Meng Lin2, 3, Li Hongyu2
1Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China; 2Guangxi Orthopedic Hospital, Nanning 530000, Guangxi Zhuang Autonomous Region, China; 3Chongqing Medical University, Chongqing 400016, China
Abstract: BACKGROUND: Observational studies have suggested that statins may have a protective effect against osteoarthritis, including knee osteoarthritis and hip osteoarthritis. However, the association between statins and the risk of osteoarthritis remains unclear.
OBJECTIVE: To investigate the association between statins and the risk of osteoarthritis through Mendelian randomization analysis using summary data from large-scale population-based genome-wide association studies (GWAS).
METHODS: Firstly, single nucleotide polymorphism data related to statins were obtained from the latest 9th edition of the FinnGen database, while data of osteoarthritis, knee osteoarthritis and hip osteoarthritis were obtained from the IEU Open GWAS, UK Biobank, and ArcOGEN (Genetics of Osteoarthritis) databases, respectively. The inverse variance weighted method was used as the primary analysis approach to evaluate the causal effects. The weighted median method, simple median method, weighted mode-based method, and MR-Egger regression were used as supplementary analyses. The causal relationship between statins and the risk of osteoarthritis, knee osteoarthritis and hip osteoarthritis was assessed using odds ratios (OR) with 95% confidence intervals (CI). Sensitivity analyses were conducted to validate the reliability of the results, including the Cochran’s Q test for heterogeneity and the MR-Egger-intercept test for horizontal pleiotropy, as well as leave-one-out analysis to identify potentially influential single nucleotide polymorphisms.
RESULTS AND CONCLUSION: The inverse variance weighted analysis demonstrated a negative causal relationship between genetically predicted statins and the risk of osteoarthritis (OR=0.998, 95% CI: 0.996-0.999, P=0.01), knee osteoarthritis (OR=0.964, 95% CI: 0.940-0.989, P=0.005), and hip osteoarthritis (OR=0.928, 95% CI: 0.901-0.955, P=4.28×10-7). MR-Egger intercept analysis did not detect potential horizontal pleiotropy (osteoarthritis: P=0.658; knee osteoarthritis: P=0.600; hip osteoarthritis: P=0.141). The results of this study provide evidence that statins reduce the risks of osteoarthritis, knee osteoarthritis and hip osteoarthritis as described in observational studies. Further research is needed to explore the specific mechanisms of statin treatment for osteoarthritis.
Key words: statins, osteoarthritis, Mendelian randomization, genome-wide association study, single nucleotide polymorphism, causal relationship