Department of Neurology & Neuro-ophthalmology, The First Hospital of Xi'an (The First Affiliated Hospital of Northwestern University), Xi'an, China.
Xi'an Key Laboratory for Innovation and Translation of Neuroimmunological Diseases, Xi'an, China.
Front Endocrinol (Lausanne). 2024 Aug 8;15:1379549. doi: 10.3389/fendo.2024.1379549. eCollection 2024.
Central retinal artery occlusion (CRAO) is a medical condition characterized by sudden blockage of the central retinal artery, which leads to a significant and often irreversible loss of vision. Observational studies have indicated that diabetes mellitus is a risk factor for CRAO; however, there is no research on the causal relationship between diabetes mellitus, particularly type 2 diabetes, and CRAO. This study aimed to perform Mendelian randomization (MR) analysis to clarify the causal relationship between type 2 diabetes and CRAO.
Genetic variants associated with type 2 diabetes were selected from two different datasets. A recent genome-wide association study of CRAO conducted using the FinnGen database was used as the outcome data. A two-sample MR was performed to evaluate the causal relationship between type 2 diabetes and CRAO. Inverse variance weighting was the primary method, and MR-Egger, maximum likelihood, and median weighting were used as complementary methods. A multivariate MR (MVMR) analysis was performed to further evaluate the robustness of the results. Cochran's Q test, MR-Egger intercept test, and MR-PRESSO global test were used for the sensitivity analyses.
Genetically predicted type 2 diabetes was causally associated with CRAO(odds ratio [OR] =2.108, 95% confidence interval [CI]: 1.221-3.638, P=7.423×10), which was consistent with the results from the validation dataset (OR=1.398, 95%CI: 1.015-1.925, P=0.040). The MVMR analysis suggested that type 2 diabetes may be an independent risk factor for CRAO (adjusted OR=1.696; 95%CI=1.150-2.500; P=7.655×10), which was assumed by the validation dataset (adjusted OR=1.356; 95%CI=1.015-1.812; P=0.039).
Our results show that genetically predicted type 2 diabetes may be causally associated with CRAO in European populations. This suggests that preventing and controlling type 2 diabetes may reduce the risk of CRAO.
中央视网膜动脉阻塞（CRAO）是一种由中央视网膜动脉突然阻塞引起的疾病，可导致显著且常不可逆的视力丧失。观察性研究表明，糖尿病是 CRAO 的一个危险因素；然而，目前还没有关于糖尿病（尤其是 2 型糖尿病）与 CRAO 之间因果关系的研究。本研究旨在进行孟德尔随机化（MR）分析，以阐明 2 型糖尿病与 CRAO 之间的因果关系。
从两个不同的数据集选择与 2 型糖尿病相关的遗传变异。使用 FinnGen 数据库进行的最近的 CRAO 全基因组关联研究被用作结局数据。进行两样本 MR 分析以评估 2 型糖尿病与 CRAO 之间的因果关系。主要方法为逆方差加权法，同时采用 MR-Egger、最大似然和中位数加权法作为补充方法。进行多变量 MR（MVMR）分析以进一步评估结果的稳健性。采用 Cochran's Q 检验、MR-Egger 截距检验和 MR-PRESSO 全局检验进行敏感性分析。
遗传预测的 2 型糖尿病与 CRAO 有因果关系（比值比[OR] =2.108，95%置信区间[CI]：1.221-3.638，P=7.423×10），与验证数据集的结果一致（OR=1.398，95%CI：1.015-1.925，P=0.040）。MVMR 分析表明，2 型糖尿病可能是 CRAO 的一个独立危险因素（调整后的 OR=1.696；95%CI=1.150-2.500；P=7.655×10），这与验证数据集的结果一致（调整后的 OR=1.356；95%CI=1.015-1.812；P=0.039）。
我们的结果表明，遗传预测的 2 型糖尿病可能与欧洲人群的 CRAO 有因果关系。这表明预防和控制 2 型糖尿病可能降低 CRAO 的风险。
