The Uric Acid and Gout have No Direct Causality With Osteoarthritis: A Mendelian Randomization Study

Abstract

Objective. To examine whether uric acid level or gout is causally associated with the risk of osteoarthritis. Methods. We performed a two-sample Mendelian randomization (MR) analysis using inverse-variance weighted (IVW), MR-Egger regression, and weighted median methods. We used the publicly available summary statistics datasets of uric acid level or gout genome-wide association studies (GWASs) as the exposure, and a GWAS in 3,498 patients with osteoarthritis in the arcOGEN study and 11,009 controls of European ancestry as the outcome. Results. Six single nucleotide polymorphisms (SNPs) from the GWAS data on uric acid level and 12 SNPs from the GWAS data on gout were selected as instrumental variables (IVs). The IVW analysis did not support a causal association between uric acid level or gout and risk of osteoarthritis (beta=-0.026, standard error [SE]=0.096, p=0.789; beta=-0.018, SE=0.025, p=0.482). MR-Egger regression revealed no causal association between uric acid level or gout and risk of osteoarthritis (beta=0.028, SE=0.142, p=0.852; beta=-0.056, SE=0.090, p=0.548). Similarly, no evidence of a casual association was provided by the weighted median approach (beta=0.004, SE=0.064, p=0.946; beta=-0.005, SE=0.025, p=0.843). Conclusion. The results of MR analysis demonstrates that uric acid level and gout may be not causally associated with the increased risk of osteoarthritis. Considering MR study is not susceptible to bias from unmeasured confounders or reverse causation, the epidemiological evidence for an association between uric acid level or gout and a higher risk of osteoarthritis may be due to residual confounding or reverse causation rather than direct causality.