Objective

The epidemiological evidence on the link between osteoarthritis (OA) and stroke remains inconclusive. Herein, we adopted a two-sample bidirectional Mendelian randomization (MR) study to determine the causality relationship between OA and stroke.

Design

Summary-level data derived from the published genome-wide association studies (GWAS) were employed for analyses. The data for OA at any site (n = 455,211), knee OA (n = 403,124), and hip OA (n = 393,873) were obtained from a meta-analysis of GWAS available in the UK Biobank and Arthritis Research UK Osteoarthritis Genetics resources. The MEGASTROKE consortium provided data for stroke (n = 446,696), ischemic stroke (IS) (n = 440,328) and its subtypes, and intracerebral hemorrhage (ICH) (n = 3,026). The main MR analysis was conducted by the inverse variance weighted (IVW) method. MR-Egger regression, MR pleiotropy residual sum and outlier, weighted median, Cochran Q statistic, and leave-one-out analysis approach were leveraged as supplements.

Results

We detected that higher risk of hip OA was significantly associated with overall stroke [IVW odds ratio (OR): 1.12, 95% confidence interval (CI): 1.06–1.20, P = 0.0002], IS (OR: 1.13, 95%CI: 1.06–1.21, P = 0.0003), and small vessel IS (OR: 1.25, 95%CI: 1.10–1.42, P = 0.0006). However, we found no evidence that stroke and subtypes had casual effects on OA in the reverse MR analyses.

Conclusions

The present study provides genetic support that hip OA is a potential risk factor for overall stroke, IS, and small vessel IS. Further studies are warranted to elucidate the underlying mechanisms of causal associations between site-specific OA and stroke subtypes.

中文翻译：

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骨关节炎和中风：双向孟德尔随机研究

客观的

关于骨关节炎 (OA) 和中风之间联系的流行病学证据尚无定论。在此，我们采用双样本双向孟德尔随机化 (MR) 研究来确定 OA 和中风之间的因果关系。

设计

来自已发表的全基因组关联研究 (GWAS) 的摘要级数据用于分析。任何部位的 OA（ n  = 455,211）、膝关节 OA（n  = 403,124）和髋关节 OA（n = 393,873）的数据 是从英国生物银行和关节炎研究英国骨关节炎遗传学资源中提供的 GWAS 荟萃分析中获得的. MEGASTROKE 联盟提供了中风 ( n  = 446,696)、缺血性中风 (IS) ( n  = 440,328) 及其亚型和脑出血 (ICH) ( n = 3,026）。主要 MR 分析通过逆方差加权 (IVW) 方法进行。MR-Egger 回归、MR 多效性残差和和异常值、加权中位数、Cochran Q 统计量和留一法分析方法被用作补充。

结果

我们检测到髋部 OA 的高风险与总体卒中显着相关 [IVW 比值比 (OR)：1.12，95% 置信区间 (CI)：1.06–1.20，P = 0.0002 ]，IS (OR：1.13，95%CI : 1.06–1.21, P = 0.0003), 小容器 IS (OR: 1.25, 95%CI: 1.10–1.42, P = 0.0006)。然而，在反向 MR 分析中，我们没有发现中风和亚型对 OA 有偶然影响的证据。

结论

本研究提供了遗传支持，即髋关节 OA 是整体卒中、IS 和小血管 IS 的潜在危险因素。需要进一步的研究来阐明特定部位的 OA 和卒中亚型之间因果关系的潜在机制。