Abstract
BACKGROUND: Vascular properties of the retina are indicative of both ocular and systemic cardio- and cerebrovascular health. However, the specific relationships between retinal and non-retinal vascular phenotypes have not been systematically investigated in large samples. This study aims to compare cross-organ phenotypic and genetic relationships between vascular characteristics across different body sites. METHODS: We compared vascular image-derived phenotypes from the brain, carotid artery, aorta, and retina, using UK Biobank sample sizes ranging from 18,808 to 68,740 participants. We examined phenotypic and genetic correlations, as well as common associated genes and pathways. RESULTS: Here we show that white matter hyperintensities are positively correlated with carotid intima-media thickness (r = 0.03), lumen diameter (r = 0.14), and aortic cross-sectional areas (r = 0.09), but negatively correlated with aortic distensibilities (r ≤ -0.05). Arterial retinal vascular density shows negative correlations with white matter hyperintensities (r = -0.04), intima-media thickness (r = -0.04), lumen diameter (r = -0.06), and aortic areas (r = -0.05), while positively correlating with aortic distensibilities (r = 0.04). Significant correlations also persist after correcting for hypertension. CONCLUSIONS: Our findings shed light on the complex interplay between vascular morphology across different organs, revealing both shared and distinct genetic underpinnings. Retinal vascular features reflect broader systemic vascular morphology and offer an accessible window into cardio- and cerebrovascular health.