Cross-organ Analysis Reveals Associations between Vascular Properties of the Retina, the Carotid and Aortic Artery, and the Brain

Vascular properties of the retina are indicative not only of ocular but also of systemic cardio- and cere-brovascular health. However, the specific relationships between retinal vascular phenotypes and those in other organs have not been systematically investigated in large samples. Here, we compared vascular image-derived phenotypes from the brain, carotid artery, aorta, and retina from the UK Biobank, with sample sizes ranging from 18,808 to 68,740 participants per phenotype. We examined the cross-organ phenotypic and genetic correlations, as well as common associated genes and pathways. White matter hyperintensities were 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 showed 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 correlated with aortic distensibilities (r=0.04). Significant correlations were also observed between other retinal phenotypes and white matter hyperintensities, as well as aortic phenotypes. Correcting for hypertension reduced the magnitude of these correlations, though the overall correlation structure persisted. Genetic correlations and gene enrichment analyses identified potential modulators of these phenotypes, with some shared genetic influence between retinal and non-retinal phenotypes. Our study sheds light on the complex interplay between vascular morphology in different organs, revealing shared and distinct genetic underpinnings, and suggesting that retinal vascular features may reflect broader vascular morphology.