Su Bingxue, Sun Yinxiang, Yu Wenlong, Wang Chaoqun, Xia Qing, Zhu Yizhun
School of Pharmacy, Zunyi Medical University, Zunyi, China.
Zhuhai People's Hospital (The First Affiliated Hospital of Faculty of Medicine Macau University of Science and Technology, The Affiliated Hospital of Beijing Institute of Technology, Zhuhai Clinical Medical College of Jinan University), Zhuhai, China.
Sci Rep. 2025 Aug 4;15(1):28357. doi: 10.1038/s41598-025-98225-3.
There is increasing evidence that eye diseases and stroke frequently co-occur, but the causal relationships remain elusive. Therefore, Mendelian randomization was used to investigate possible causal relationships between eye diseases and stroke (including its subtypes). This study utilized large-scale genome-wide association study pooled genetic data from two major databases: the IEU OpenGWAS project and the FinnGen databases. We then screened for instrumental variables that met the following three conditions: showing strong associations with the exposure factors, being independent of each other and independent of any confounders, and excluding instrumental variables to ensure that the F-value was greater than 10, and used the Inverse Variance Weighted (IVW) method to conduct causal analyses using the weighted median method, MR-Egger method, MR- PRESSO test and leave-one-out sensitivity test to test the robustness, heterogeneity and horizontal pleiotropy of the results. In order to control for the false positive rate in multiple hypothesis testing, a False Discovery Rate (FDR) correction was also performed. A total of 16 eye diseases and strokes and their subtypes were investigated in this study. In the IVW model, the MR study showed a total of 20 IVWs with p-values less than 0.05. We excluded 6 results with heterogeneity or pleiotropy by sensitivity analysis, and finally the following reliable results were left: (1) patients with age-related macular degeneration had a 5%, 2%, and 7% lower risk of subarachnoid hemorrhage, ischemic stroke, and small-vessel stroke; (2) patients with keratitis had a 12% higher risk of cardioembolic; (3) patients with optic atrophy had a 3% higher risk of stroke; (4) patients with amblyopia had a 3% higher risk of stroke; and (5) patients with other inflammation of eyelid had a small-vessel had a 20% elevated risk; (6) patients with ptosis of the eye had a 17% elevated risk of cardioembolic; (7) patients with strabismus have a 23% elevated risk of small-vessel; (8) patients with stroke had a refractive error by 17%; (9) patients with intracerebral hemorrhage had a 15% increased risk of uveitis; (10) patients with IS had an 11% increased risk of diabetic retinopathy; (11) patients with large-artery atherosclerosis had a 2% increased risk of glaucoma; (12) patients with cardioembolic had a 24% increased risk of amblyopia. From a genetic standpoint, keratitis, amblyopia, other eyelid inflammations, ptosis and strabismus are associated with increased risks of the risk of stroke or its subtypes. Conversely, age-related macular degeneration is associated with reduced risks of the risk of stroke or its subtypes. Furthermore, stroke or its subtypes increase the risks of refractive error, uveitis, diabetic retinopathy, glaucoma, and amblyopia. Nevertheless, it is imperative that these causal relationships be subjected to further verification through fundamental research and Randomized Controlled Trial (RCT).
越来越多的证据表明,眼部疾病和中风经常同时发生,但因果关系仍不明确。因此,采用孟德尔随机化方法来研究眼部疾病与中风(包括其亚型)之间可能存在的因果关系。本研究利用了来自两个主要数据库(IEU OpenGWAS项目和芬兰基因组数据库)的大规模全基因组关联研究汇总遗传数据。然后,我们筛选出符合以下三个条件的工具变量:与暴露因素有强关联、相互独立且独立于任何混杂因素,并排除工具变量以确保F值大于10,使用逆方差加权(IVW)方法,采用加权中位数法、MR-Egger法、MR-PRESSO检验和留一法敏感性检验来进行因果分析,以检验结果的稳健性、异质性和水平多效性。为了控制多重假设检验中的假阳性率,还进行了错误发现率(FDR)校正。本研究共调查了16种眼部疾病、中风及其亚型。在IVW模型中,孟德尔随机化研究显示共有20个IVW的p值小于0.05。通过敏感性分析,我们排除了6个存在异质性或多效性的结果,最终得到以下可靠结果:(1)年龄相关性黄斑变性患者发生蛛网膜下腔出血、缺血性中风和小血管中风的风险分别降低5%、2%和7%;(2)角膜炎患者发生心源性栓塞的风险升高12%;(3)视神经萎缩患者发生中风的风险升高3%;(4)弱视患者发生中风的风险升高3%;(5)其他眼睑炎症患者发生小血管中风的风险升高20%;(6)眼睑下垂患者发生心源性栓塞的风险升高17%;(7)斜视患者发生小血管中风的风险升高23%;(8)中风患者发生屈光不正的风险升高17%;(9)脑出血患者发生葡萄膜炎的风险升高15%;(10)缺血性中风患者发生糖尿病视网膜病变的风险升高11%;(11)大动脉粥样硬化患者发生青光眼的风险升高2%;(12)心源性栓塞患者发生弱视的风险升高24%。从遗传学角度来看,角膜炎、弱视、其他眼睑炎症、眼睑下垂和斜视与中风或其亚型风险的增加有关。相反,年龄相关性黄斑变性与中风或其亚型风险的降低有关。此外,中风或其亚型会增加屈光不正、葡萄膜炎、糖尿病视网膜病变、青光眼和弱视的风险。然而,这些因果关系必须通过基础研究和随机对照试验(RCT)进行进一步验证。
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