Assessing causality between osteoarthritis with urate levels and gout: a bidirectional Mendelian randomization study

Abstract

The bidirectional association between osteoarthritis (OA) and urate levels and gout, though well-documented, is inconclusive. This Mendelian randomization (MR) study aims to examine the bidirectional causality between OA and urate levels as well as gout. We used summary statistics data for serum urate levels from 288,649 CKDGen participants and gout from 69,374 Global Urate Genetics Consortium participants. The summary statistics data for OA were obtained from genome-wide association studies including up to 826,690 participants of mainly European ancestry. MR was performed using established analytical methods including the Wald ratio, inverse variance weighted (IVW), weighted median (WM) and MR-Egger. Genetically determined urate levels [IVW odds ratio (OR)=0.99, 95% confidence interval (CI)=0.96, 1.02, P=0.484] and gout (Wald ratio OR=1.00, 95% CI=0.98, 1.02, P=0.908) were not associated with the risk of total OA. In site-specific OA analyses, there was no causal effect of urate levels on knee, hip, spine, thumb and hand OA, and no evidence was provided that gout increased the risk of OA at any site. In the reverse MR analyses, we found no causal effect of total OA on urate levels (IVW Beta=-0.011, 95% CI=-0.095, 0.074, P=0.807) or gout (IVW OR=1.05, 95% CI=0.66, 1.68, P=0.839). A null effect of site-specific OA was also observed. Our MR study supports no bidirectional causal effect of urate levels and gout on total and site-specific OA.