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髋骨关节炎与腔隙性脑卒风险:两样本孟德尔随机化研究。

Hip Osteoarthritis and the Risk of Lacunar Stroke: A Two-Sample Mendelian Randomization Study.

机构信息

Department of Epidemiology & Health Statistics, School of Public Health, Nantong University, Nantong 226019, China.

Center for Disease Control and Prevention of Nantong, Nantong 226007, China.

出版信息

Genes (Basel). 2022 Sep 3;13(9):1584. doi: 10.3390/genes13091584.

Abstract

Whether hip osteoarthritis (OA) could increase the risk of lacunar stroke (LS) is not well understood. This two-sample Mendelian randomization (MR) study aimed to investigate in depth the effect of genetically predicted hip OA on LS risk. Hip OA-related instrumental variables (IVs) were selected from a genome-wide association study (GWAS) of 393,873 individuals. The summary data of LS were obtained from a GWAS meta-analysis, including 16,030 cases and 248,929 controls. We used the inverse-variance weighted (IVW) as the primary MR analysis method. Moreover, the weighted-median, MR-Egger regression, and the MR pleiotropy residual sum and outlier (MR-PRESSO) test were supplementary methods. The sensitivity analysis was performed using the leave-one-out test. We identified the positive causal relationship between hip OA and the risk of LS (odds ratio [OR] = 1.20, 95% confidence interval [CI]: 1.07, 1.36; = 0.002 using the IVW method). The weighted median method provided similar results. There was no evidence of directed pleiotropy, and sensitivity analysis results were stable, suggesting the robustness of our study. This study showed a causal effect of hip OA on the risk of LS, and more efforts should be made to explore the potential mechanisms in the future.

摘要

髋骨关节炎(OA)是否会增加腔隙性卒中(LS)的风险尚不清楚。本项两样本孟德尔随机化(MR)研究旨在深入探讨遗传预测的髋骨 OA 对 LS 风险的影响。从一项包含 393873 人的全基因组关联研究(GWAS)中选择了与髋骨 OA 相关的工具变量(IVs)。LS 的汇总数据来自一项 GWAS 荟萃分析,其中包括 16030 例病例和 248929 例对照。我们使用逆方差加权(IVW)作为主要的 MR 分析方法。此外,加权中位数、MR-Egger 回归和 MR 多效性残差总和和异常值(MR-PRESSO)检验是补充方法。敏感性分析采用了逐一剔除的方法。我们确定了髋骨 OA 与 LS 风险之间存在正向因果关系(比值比 [OR] = 1.20,95%置信区间 [CI]:1.07,1.36;IVW 方法的 P 值= 0.002)。加权中位数方法提供了类似的结果。没有证据表明存在定向多效性,敏感性分析结果稳定,表明本研究具有稳健性。本研究表明髋骨 OA 与 LS 风险之间存在因果关系,未来应进一步努力探索潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a309/9498627/2ef6437e2000/genes-13-01584-g001.jpg

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