School of Public Health, Hangzhou Medical College, Hangzhou, 310053, China.
Department of Orthopaedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Osteoarthritis Cartilage. 2022 Apr;30(4):551-558. doi: 10.1016/j.joca.2021.12.001. Epub 2021 Dec 8.
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.
尽管已经充分证明骨关节炎（OA）与尿酸水平和痛风之间存在双向关联，但这种关联尚无定论。本孟德尔随机化（MR）研究旨在检验 OA 与尿酸水平以及痛风之间的双向因果关系。
我们使用了 288649 名 CKDGen 参与者的血清尿酸水平和 69374 名全球尿酸遗传学联合会参与者的痛风的汇总统计数据。OA 的汇总统计数据来自全基因组关联研究，这些研究包括了主要来自欧洲血统的多达 826690 名参与者。使用已建立的分析方法（包括 Wald 比值、逆方差加权（IVW）、加权中位数（WM）和 MR-Egger）进行 MR。
遗传决定的尿酸水平[IVW 比值比（OR）=0.99，95%置信区间（CI）=0.96，1.02，P=0.484]和痛风（Wald 比值 OR=1.00，95%CI=0.98，1.02，P=0.908）与总 OA 风险无关。在特定部位 OA 分析中，尿酸水平对膝关节、髋关节、脊柱、拇指和手部 OA 没有因果影响，也没有证据表明痛风会增加任何部位 OA 的风险。在反向 MR 分析中，我们发现总 OA 对尿酸水平（IVW Beta=-0.011，95%CI=-0.095，0.074，P=0.807）或痛风（IVW OR=1.05，95%CI=0.66，1.68，P=0.839）没有因果影响。特定部位 OA 的影响也呈零效应。
我们的 MR 研究支持尿酸水平和痛风与总部位和特定部位 OA 之间不存在双向因果关系。
