Multi-omic analysis of deep learning-derived phenotypes links ophthalmic imaging to cardiovascular and neurological traits
The eye is a recognized source of biomarkers for cardiovascular and neurodegenerative disease risk. Here we characterize the breadth of these associations and identify biological axes that may mediate them. Using UK Biobank data, we developed a multi-omic analysis pipeline integrating physiological, radiomic, metabolomic and genomic information. We trained retinal adversarial autoencoders to represent optical coherence tomography images and color fundus photographs as 256-dimensional embeddings. Retinal adversarial autoencoder-derived embeddings were associated with a range of cardiovascular and neurodegenerative diseases, including ischemic heart disease, cerebrovascular disease, Parkinson's disease and dementia. Examining associations across diverse omics datasets, we provide evidence linking ophthalmic imaging features to neurological and cardiovascular anatomy and function, lipid metabolism and gene sets associated with neurodegenerative pathology. Collectively, our findings show that ophthalmic features reflect complex, multisystem biological processes and reinforce the role of the eye as a composite indicator of systemic health.
Authors
- Pearse A. Keane (ORCID: https://orcid.org/0000-0002-9239-745X)
- Tomas Fitzgerald (ORCID: https://orcid.org/0000-0002-2370-8496)
- Matthew Sperrin (ORCID: https://orcid.org/0000-0002-5351-9960)
- Elham Alhathli (ORCID: https://orcid.org/0009-0008-2147-9715)
- Thomas Julian (ORCID: https://orcid.org/0000-0002-5488-5620)
- A. Strange (ORCID: https://orcid.org/0000-0002-2004-150X)
- Bernard D. Keavney (ORCID: https://orcid.org/0000-0001-9573-0812)
- Johnathan Cooper‐Knock (ORCID: https://orcid.org/0000-0002-0873-8689)
- Alejandro Federico Frangi (ORCID: https://orcid.org/0000-0002-2675-528X)
- Ewan Birney (ORCID: https://orcid.org/0000-0001-8314-8497)
- Jinming Duan (ORCID: https://orcid.org/0000-0002-5108-2128)
- Panagiotis I. Sergouniotis
- Esther Yoo (ORCID: https://orcid.org/0000-0001-8759-0098)
- Haoran Dou (ORCID: https://orcid.org/0000-0001-8628-5489)
- Emily Y. Chew (ORCID: https://orcid.org/0000-0003-0999-9802)
- David Green (ORCID: https://orcid.org/0000-0002-7408-058X)
- Jinghan Huang (ORCID: https://orcid.org/0009-0009-7847-6635)
Institutions
- National Institutes of Health (US)
- European Bioinformatics Institute (GB)
- Moorfields Eye Hospital NHS Foundation Trust (GB)
- Manchester Academic Health Science Centre (GB)
- Universitair Ziekenhuis Leuven (BE)
- Manchester Royal Eye Hospital (GB)
- University of Manchester (GB)
- Manchester University NHS Foundation Trust (GB)
- National Eye Institute (US)
- Moorfields Eye Hospital (GB)
- Genomics (United Kingdom) (GB)
- NIHR Manchester Biomedical Research Centre (GB)
- University College London (GB)
- University of Sheffield (GB)
- KU Leuven (BE)
Publication Details
- Journal
- Nature Cardiovascular Research
- Published
- 2026-06-16
- DOI
- https://doi.org/10.1038/s44161-026-00815-5
- Primary Topic
- Retinal Imaging and Analysis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Wellcome Trust
- European Bioinformatics Institute
- UK Research and Innovation
- National Institute for Health and Care Research
- British Heart Foundation
- Royal Academy of Engineering
- Motor Neurone Disease Association
- Moorfields Eye Charity
- Manchester Biomedical Research Centre
- Medical Research Council
- Alcon Research Institute