Genetic Architecture of Choroidal Vascularity Revealed by Population-scale Retinal Imaging

Genetic Architecture of Choroidal Vascularity Revealed by Population-scale Retinal Imaging | Research Square Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Genetic Architecture of Choroidal Vascularity Revealed by Population-scale Retinal Imaging Camille Pittet, Leah Böttger, Chiara M Eandi, Laura Mauring, Andrea Montesel, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8842359/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background and Aim: The choroid is a highly vascular tissue essential for retinal homeostasis, and its remodeling particularly venous congestion is a hallmark of pachychoroid diseases such as central serous chorioretinopathy. The choroidal vascularity index (CVI), a quantitative ratio of vascular to total choroidal area derived from optical coherence tomography (OCT), captures inter-individual variation in choroidal vascular structure. However, the genetic determinants of CVI and their biological implications remain unknown. Here, we aimed to define the genetic architecture of CVI using population-scale OCT imaging. Methods: We developed a scalable automated pipeline integrating image processing and rule-based vessel segmentation to extract three-dimensional CVI phenotypes from macular OCT volumes. We applied this framework to OCT data from 62,751 UK Biobank participants after quality control. Genome-wide association studies were performed for CVI mean and spatial variability, adjusting for demographic, ocular, and genetic covariates. Associated loci were interpreted using gene-based analyses. Results: We identified 12 independent loci across nine chromosomes associated with CVI traits. CVI mean was enriched for loci linked to systemic vascular and hematologic pathways, including ABO and VWF, whereas CVI variability showed stronger associations with inflammatory and complement-related genes, notably CFH, previously implicated central serous chorioretinopathy, a pachychoroid disease. Additional loci highlighted roles for mitochondrial function, metabolism, pigmentation, and oxidative stress. Conclusion: Our results establish CVI as a heritable imaging endophenotype and reveal distinct genetic contributions to average choroidal vascularity and its spatial heterogeneity. These findings link choroidal vascular remodeling to systemic vascular, inflammatory, and metabolic pathways, providing a framework for integrating ocular imaging with genetic studies of microvascular disease. Bioinformatics Choroidal vascularity index genome-wide association study imaging genetics optical coherence tomography microvascular remodeling Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information

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