Systemic lupus erythematosus increases the risk of knee osteoarthritis: A Mendelian randomization study

Abstract

Abstract Patients with systemic lupus erythematosus (SLE) often present with musculoskeletal system involvement, but the existence of a causal association between SLE and osteoarthritis remains unclear. Knee osteoarthritis (KOA) is the most common form of osteoarthritis. We used two-sample Mendelian randomization to analyze the potential causal relationship between SLE and KOA risk. We downloaded summary data on SLE and KOA from the IEU Open genome-wide association studies database and selected 52 single nucleotide polymorphisms that were independently associated with SLE as genetic IVs. Inverse variance weighted, MR-Egger, weighted median, simple model, and weighted model methods were selected for two-sample Mendelian randomization analysis. Pleiotropy was estimated using MR-Egger regression, MR-PRESSO, and Cochran's Q tests. Finally, sensitivity analysis was performed using the leave-one-out method. The results of all five models showed a significant causal association between SLE and KOA. SLE increased the risk of KOA (odds ratio = 1.012, 95% confidence interval = 1.002–1.023, P = 0.017 using inverse variance weighted analysis), and no significant polymorphism was found. Sensitivity analysis supported that the results were robust. In summary, our study reveals that SLE is an important risk factor for KOA and a potential causal association exists between SLE and KOA. Therefore, controlling SLE may be important for the prevention of KOA.