Jiang Bingcai, Wei Xin, Cao Xiaochuan, Zheng Changwei
Department of Ophthalmology, Guizhou Provincial People's Hospital, Guizhou, China.
Department of Ophthalmology, The People's Hospital of Tongliang District, Chongqing, China.
Medicine (Baltimore). 2025 May 2;104(18):e41752. doi: 10.1097/MD.0000000000041752.
Understanding the etiological risk factors for retinal vascular occlusion (RVO) is critical for prevention and treatment. While the effects of cardiovascular events, hypertension, glaucoma, obesity and glycemic risk factors on RVO are still controversial. This study employed two-sample Mendelian randomization (MR) analysis to investigate these causal risk factors. Single-nucleotide polymorphisms (SNPs) were used as instrumental variables (IVs). Genetic instruments for hypertension, glaucoma, obesity, cardiovascular events and glycemic risk factors were obtained from published genome-wide association studies (GWASs). Summary-level data for RVO and hypertension were obtained from the FinnGen consortium. MR analysis primarily utilized the inverse variance weighted (IVW) method, with MR-Egger and weighted median as supplementary approaches. Multivariable MR (MVMR) adjusting for hypertension or glaucoma of RVO were conducted. Heterogeneity was assessed using Cochrane's Q test and I2, while MR-Egger intercept and MR-PRESSO tested horizontal pleiotropy. All MR analyses were performed within R software (4.1.3) using the R packages "TwoSampleMR" and "MR-PRESSO." Genetic instruments for hypertension and glaucoma were significantly associated with RVO risk. A one-standard deviation (SD) increase in hypertension was associated with a higher risk of RVO [OR = 1.577, 95% CI = (1.342, 1.854), P < .001], while a one-SD increase in the log odds of genetically predicted glaucoma was associated with a higher risk of RVO [OR = 1.24, 95% CI = (1.115, 1.379), P < .001]. Meanwhile, hypertension and glaucoma were still significant in multivariable MR. There was not sufficient evidence to suggest cardiovascular events and obesity were associated with RVO risk. This MR study provided genetic evidence supporting that hypertension and glaucoma were causally associated with the risk of RVO. It may help guide clinical decisions in the management of RVO patients with hypertension and glaucoma.
了解视网膜血管阻塞（RVO）的病因风险因素对于预防和治疗至关重要。虽然心血管事件、高血压、青光眼、肥胖和血糖风险因素对RVO的影响仍存在争议。本研究采用两样本孟德尔随机化（MR）分析来探究这些因果风险因素。单核苷酸多态性（SNP）用作工具变量（IV）。高血压、青光眼、肥胖、心血管事件和血糖风险因素的遗传工具来自已发表的全基因组关联研究（GWAS）。RVO和高血压的汇总数据来自芬兰基因组联盟。MR分析主要采用逆方差加权（IVW）方法，以MR-Egger和加权中位数作为补充方法。进行了针对RVO的高血压或青光眼调整的多变量MR（MVMR）分析。使用Cochrane's Q检验和I2评估异质性，而MR-Egger截距和MR-PRESSO检验水平多效性。所有MR分析均在R软件（4.1.3）中使用R包“TwoSampleMR”和“MR-PRESSO”进行。高血压和青光眼的遗传工具与RVO风险显著相关。高血压每增加一个标准差（SD）与RVO风险升高相关[比值比（OR）=1.577，95%置信区间（CI）=(1.342, 1.854)，P<0.001]，而遗传预测青光眼的对数优势比每增加一个SD与RVO风险升高相关[OR=1.24，95%CI=(1.115, 1.379)，P<0.001]。同时，在多变量MR中高血压和青光眼仍然显著。没有足够的证据表明心血管事件和肥胖与RVO风险相关。这项MR研究提供了遗传证据，支持高血压和青光眼与RVO风险存在因果关系。它可能有助于指导对患有高血压和青光眼的RVO患者的临床管理决策。
