Phenotypic and genetic characteristics of retinal vascular parameters and their association with diseases

Fundus images allow for non-invasive assessment of the retinal vasculature whose features provide important information on health. Using a fully automated image processing pipeline, we extract 17 different morphological vascular phenotypes, including median vessels diameter, diameter variability, main temporal angles, vascular density, central retinal equivalents, the number of bifurcations, and tortuosity, from over 130,000 fundus images of close to 72,000 UK Biobank subjects. We perform genome-wide association studies of these phenotypes. From this, we estimate their heritabilities, ranging between 5 and 25%, and genetic cross-phenotype correlations, which mostly mirror the corresponding phenotypic correlations, but tend to be slightly larger. Projecting our genetic association signals onto genes and pathways reveals remarkably low overlap suggesting largely decoupled mechanisms modulating the different phenotypes. We find that diameter variability, especially for the veins, associates with diseases including heart attack, pulmonary embolism, and age of death. Mendelian Randomization analysis suggests a causal influence of blood pressure and body mass index on retinal vessel morphology, among other results. We validate key findings in two independent smaller cohorts. Our analyses provide evidence that large-scale analysis of image-derived vascular phenotypes has sufficient power for obtaining functional and causal insights into the processes modulating the retinal vasculature.

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Publication Details

Journal
Nature Communications
Published
2024-11-06
DOI
https://doi.org/10.1038/s41467-024-52334-1
Citations
24
Primary Topic
Retinal Imaging and Analysis
Type
article
Field-Weighted Citation Impact
9.70

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article

Phenotypic and genetic characteristics of retinal vascular parameters and their association with diseases

Wishal D. Ramdas, Bart Liefers, Caroline C. W. Klaver, Sofía Ortín Vela et al.
24 citations
Nature Communications
Retinal Imaging and Analysis
9.70
article

Phenotypic and genetic characteristics of retinal vascular parameters and their association with diseases

Wishal D. Ramdas, Bart Liefers, Caroline C. W. Klaver, Sofía Ortín Vela, Olga Trofimova, Ilaria Iuliani, Michael J. Beyeler, Victor A. de Vries, Reinier O. Schlingemann, Mattia Tomasoni, Sven Bergmann, David M. Presby, Florence Hoogewoud, Adham Elwakil, Jose D. Vargas Quiros, Ilenia Meloni
article en
24 citations

Abstract

Fundus images allow for non-invasive assessment of the retinal vasculature whose features provide important information on health. Using a fully automated image processing pipeline, we extract 17 different morphological vascular phenotypes, including median vessels diameter, diameter variability, main temporal angles, vascular density, central retinal equivalents, the number of bifurcations, and tortuosity, from over 130,000 fundus images of close to 72,000 UK Biobank subjects. We perform genome-wide association studies of these phenotypes. From this, we estimate their heritabilities, ranging between 5 and 25%, and genetic cross-phenotype correlations, which mostly mirror the corresponding phenotypic correlations, but tend to be slightly larger. Projecting our genetic association signals onto genes and pathways reveals remarkably low overlap suggesting largely decoupled mechanisms modulating the different phenotypes. We find that diameter variability, especially for the veins, associates with diseases including heart attack, pulmonary embolism, and age of death. Mendelian Randomization analysis suggests a causal influence of blood pressure and body mass index on retinal vessel morphology, among other results. We validate key findings in two independent smaller cohorts. Our analyses provide evidence that large-scale analysis of image-derived vascular phenotypes has sufficient power for obtaining functional and causal insights into the processes modulating the retinal vasculature.

Nature CommunicationsVol. 15(1)
SIB Swiss Institute of Bioinformatics (CH), Radboud University Nijmegen (NL), University of Cape Town (ZA), University of Basel (CH), Erasmus MC (NL), Radboud University Medical Center (NL), Fondation Asile des Aveugles (CH), Amsterdam University Medical Centers (NL), Institute of Molecular and Clinical Ophthalmology Basel (CH), University of Lausanne (CH)
National Science Foundation, European Commission, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, ZonMw, Erasmus Medisch Centrum, Oogfonds, Landelijke Stichting voor Blinden en Slechtzienden, Stichting voor Ooglijders
Good health and well-being
Openalex Percentile: Top 1%
Retinal Imaging and Analysis
9.70
DOIOpen Access PDFOpenAlex
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