Objectives

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.

Methods

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.

Results

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.

Conclusion

Our MR study supports no bidirectional causal effect of urate levels and gout on total and site-specific OA.

中文翻译：

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评估骨关节炎与尿酸盐水平和痛风之间的因果关系：双向孟德尔随机化研究

目标

骨关节炎 (OA) 与尿酸盐水平和痛风之间的双向关联虽然有充分的证据，但尚无定论。这项孟德尔随机化 (MR) 研究旨在检查 OA 和尿酸盐水平以及痛风之间的双向因果关系。

方法

我们使用了来自 288,649 名 CKDGen 参与者和来自 69,374 名全球尿酸盐遗传学联盟参与者的痛风的血清尿酸盐水平的汇总统计数据。OA 的汇总统计数据来自全基因组关联研究，其中包括多达 826,690 名主要欧洲血统的参与者。MR 是使用已建立的分析方法进行的，包括 Wald 比率、逆方差加权 (IVW)、加权中位数 (WM) 和 MR-Egger。

结果

基因决定的尿酸盐水平 [IVW 优势比 (OR) = 0.99, 95% 置信区间 (CI) = 0.96, 1.02, P  = 0.484] 和痛风 (Wald 比 OR = 1.00, 95% CI = 0.98, 1.02, P  = 0.908 ) 与总 OA 的风险无关。在特定部位的 OA 分析中，尿酸盐水平对膝关节、髋关节、脊柱、拇指和手部 OA 没有因果关系，也没有证据表明痛风会增加任何部位的 OA 风险。在反向 MR 分析中，我们发现总 OA 对尿酸盐水平（IVW Beta = -0.011, 95% CI = -0.095, 0.074, P  = 0.807）或痛风（IVW OR = 1.05, 95% CI = 0.66）没有因果关系, 1.68, P  = 0.839)。还观察到位点特异性 OA 的无效效应。

结论

我们的 MR 研究不支持尿酸盐水平和痛风对总和特定部位 OA 的双向因果影响。