The early detection of cardiovascular events is a key strategy for controlling and reducing its leading and increasing morbidity and mortality worldwide. The integration of novel technological and scientific advances has been central for early identifying the pathogenesis of this multifactorial disease, and this is certainly the case of the retina. The retina is the innermost layer of the eye unique in allowing the observation of the vascular system in vivo using noninvasive imaging modalities. By implementing semi-automated software, retinal images can provide phenotypes that capture the structure of the vascular network, such as the branching pattern. There is increasing evidence that the retinal branching pattern, also named retinal vascular complexity, might offer earlier insights into the progression of major cardiovascular diseases than established risk factors. Thus, retinal vascular complexity could be a promising noninvasive biomarker for fatal cardiovascular events, such as myocardial infarction and stroke.
Population-based studies demonstrated that retinal vascular phenotypes have a genetic basis, where associated loci also contribute to cardiovascular physiology and pathology. Evidence points towards a shared genetic basis plausibly influencing the equivalent pathophysiological variations in the retinal and global vascular system at early ischaemic stages. However, there is little information about the genetic component that underlies the retinal vascular complexity and its associated mechanisms common to general vascular health. Elucidating these genetic mechanisms is of great importance, as it could lead to a better understanding of the regulation of retinal and major vascular systems and, consequently, substantiate the future application of retinal vascular complexity as an intermediary of systemic vascular health.
This study comprehensively analysed retinal vascular complexity by integrating epidemiological, genetic, and translational disciplines. To this end, we obtained retinal vascular complexity from retinal fundus images and demographic, clinical, and genotyping information from approximately 38,800 individuals with white-British ancestry, 5,000 individuals with white European ancestry, 500 individuals with Asian ancestry and 500 individuals with African ancestry from the UK Biobank. We found nine loci contributing to retinal vascular complexity that were previously reported in genetic studies of ocular and cardiovascular disease. Functional and enrichment analyses indicated that these loci regulate transcriptional mechanisms central to the development and physiology of the retinal vasculature and influence global vascular pathology.
Overall, this study delved into the genetic component of retinal vascular complexity, describing part of its genetic mechanisms and its association with global vascular genetics. Our findings are consistent with previous reports, suggesting that retinal vascular complexity has an intricate shared genetic basis with cardiovascular conditions. This study ultimately sheds new light on the value of highly accessible vascular imaging phenotypes and their promising application in personalised medicine.
Date made available30 Jul 2023
PublisherEdinburgh DataShare
Temporal coverage1 Sept 2018 - 30 Nov 2022
Geographical coverageUK,UNITED KINGDOM

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