Niu Yongyi, Li Xue, Guo Jingze, Luo Songyuan, Shang Xianwen, Liu Jing, Liu Shunming, He Mingguang, Shi Danli, Huang Yu, Zhang Hongyang
Department of Ophthalmology, Guangdong Provincial People's Hospital of Southern Medical University, Guangzhou, 510080 China.
The First School of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515 China.
EPMA J. 2025 May 6;16(2):401-417. doi: 10.1007/s13167-025-00411-w. eCollection 2025 Jun.
Retinal vessel caliber is strongly associated with systemic blood pressure (BP); however, the causal relationship between retinal vascular caliber and BP remains unclear. Understanding this relationship is essential for advancing predictive, preventive, and personalized medicine (PPPM) approaches to effectively manage hypertension and its related complications.
Microvessel morphology is causally related to blood pressure. By integrating genome-wide association studies, Mendelian randomization analysis, transcriptomic data, and multivariate genomic approaches, this study aims to identify predictive biomarkers, uncover preventive strategies, and develop personalized intervention targets, thereby advancing the principles of 3P medicine for improved cardiovascular health management.
We conducted a comprehensive investigation into the genetic factors underlying retinal vessel calibers and their complex relationship with BP traits. Our genome-wide association study (GWAS) assess retinal vessel calibers-central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), and the arteriole-to-venule ratio (AVR)-in a subset of 36,223 individuals of European descent from the UK Biobank. The analysis identified 9, 5, and 4 SNPs located in , , , , , , , , , , , , and region, which are significantly associated with CRAE, CRVE, and AVR, respectively. Genetic correlation analysis revealed shared heritability between BP traits and both CRAE and AVR, but not CRVE. Mendelian randomization analysis confirmed bidirectional causal relationships between CRAE and BP traits, whereas CRVE was neither influenced by nor influenced BP traits. To explore the potential regulatory mechanisms, we leveraged transcriptomic data and identified the following causal pathways in vessel tissue: The expression of MRPL23-AS1 and ULK3 was correlated with the elevation of blood pressure SBP and narrowing of the CRAE. Finally, we constructed a multivariable genetic model including CRAE, AVR, SBP, and DBP, suggesting a common driving factor which underlies these traits.
Our study elucidates the complex relationship between BP and retinal vessel caliber, highlighting potential intervention targets for lowering BP and vascular narrowing-related diseases. These findings contribute to the development of tailored prevention and treatment strategies aligned with PPPM principles.
The online version contains supplementary material available at 10.1007/s13167-025-00411-w.
视网膜血管管径与全身血压（BP）密切相关；然而，视网膜血管管径与血压之间的因果关系仍不明确。了解这种关系对于推进预测性、预防性和个性化医学（PPPM）方法以有效管理高血压及其相关并发症至关重要。
微血管形态与血压存在因果关系。通过整合全基因组关联研究、孟德尔随机化分析、转录组数据和多变量基因组方法，本研究旨在识别预测性生物标志物，揭示预防策略，并制定个性化干预靶点，从而推进3P医学原则以改善心血管健康管理。
我们对视网膜血管管径的遗传因素及其与血压特征的复杂关系进行了全面调查。我们的全基因组关联研究（GWAS）在英国生物银行中36223名欧洲血统个体的子集中评估了视网膜血管管径——视网膜中央动脉等效直径（CRAE）、视网膜中央静脉等效直径（CRVE）以及动静脉比（AVR）。分析确定了分别位于、、、、、、、、、、、区域的9个、5个和4个单核苷酸多态性（SNP），它们分别与CRAE、CRVE和AVR显著相关。遗传相关性分析揭示了血压特征与CRAE和AVR之间存在共同遗传性，但与CRVE不存在。孟德尔随机化分析证实了CRAE与血压特征之间的双向因果关系，而CRVE既不受血压特征影响，也不影响血压特征。为了探索潜在的调控机制，我们利用转录组数据并在血管组织中确定了以下因果途径：MRPL23 - AS1和ULK3的表达与收缩压（SBP）升高和CRAE变窄相关。最后，我们构建了一个包括CRAE、AVR、SBP和舒张压（DBP）的多变量遗传模型，表明这些特征存在一个共同的驱动因素。
我们的研究阐明了血压与视网膜血管管径之间的复杂关系，突出了降低血压和血管狭窄相关疾病的潜在干预靶点。这些发现有助于制定符合PPPM原则的个性化预防和治疗策略。
在线版本包含可在10.1007/s13167 - 025 - 00411 - w获取的补充材料。
