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 not only indicative of ocular but also systemic cardio– and cerebrovascular health. Yet, the extent to which retinal vascular morphology reflects that in other organs is not well understood. We used morphological vascular phenotypes derived from the brain, the carotid artery, the aorta, and the retina from the UK Biobank, with sample sizes between 33,000 and 68,000 subjects per phenotype. We examined the cross-organ phenotypic and genetic correlations, as well as common associated genes and pathways. White matter hyperintensities positively correlated with carotid intima-media thickness and aortic cross-sectional areas but negatively correlated with aortic distensibility. Retinal vascular density showed negative correlations with white matter hyperintensities, intima-media thickness, and aortic areas, while positively correlating with aortic distensibility. Significant correlations were also observed between other retinal phenotypes and white matter hyperintensities, as well as with aortic phenotypes. Correcting for hypertension reduced the magnitude of these correlations, but the overall correlation structure largely persisted. Genetic correlations and gene enrichment analyses identified potential regulators 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 across different organs, revealing both shared and distinct genetic underpinnings. This highlights the potential of retinal imaging as a non-invasive prognostic tool for systemic vascular health.