Brain–heart–eye axis revealed by multi-organ imaging genetics and proteomics
Multi-organ research investigates interconnections among multiple human organ systems, enhancing our understanding of human aging and disease mechanisms. Here we use multi-organ imaging, individual- and summary-level genetics, and proteomics data consolidated via the MULTI Consortium to delineate a brain-heart-eye axis using brain patterns of structural covariance (PSCs), heart imaging-derived phenotypes (IDPs) and eye IDPs. We find that proteome-wide associations of the PSCs and IDPs show within-organ specificity and cross-organ interconnections. Pleiotropic effects of common single-nucleotide polymorphisms are observed across multiple organs, and key genetic parameters are estimated for single-nucleotide polymorphism-based heritability, polygenicity and selection signatures across the three organs. A gene-drug-disease network shows the potential of drug repurposing for cross-organ diseases. Co-localization and causal analyses reveal cross-organ causal relationships between PSC/IDP and chronic diseases, such as Alzheimer's disease, heart failure and glaucoma. Finally, integrating multi-organ/omics features improves prediction for systemic disease categories and cognition compared with single-organ/omics features, providing future avenues for modelling human aging and disease.
Authors
- Aleix Boquet-Pujadas (ORCID: https://orcid.org/0000-0002-3300-8004)
- Arthur W. Toga (ORCID: https://orcid.org/0000-0001-7902-3755)
- Michael S. Rafii (ORCID: https://orcid.org/0000-0003-2640-2094)
- Andrew Zalesky (ORCID: https://orcid.org/0000-0003-2298-9908)
- Paul S. S Aisen (ORCID: https://orcid.org/0000-0002-2896-5838)
- Jian Zeng (ORCID: https://orcid.org/0000-0001-8801-5220)
- Christos A. Davatzikos (ORCID: https://orcid.org/0000-0002-1025-8561)
- Luigi Ferrucci (ORCID: https://orcid.org/0000-0002-6273-1613)
- Michael R. Duggan (ORCID: https://orcid.org/0000-0002-1029-4423)
- Wenjia Bai (ORCID: https://orcid.org/0000-0003-2943-7698)
- Keenan A. Walker (ORCID: https://orcid.org/0000-0002-5989-9853)
- Ye Tian (ORCID: https://orcid.org/0000-0003-3107-5550)
- Filippos Anagnostakis (ORCID: https://orcid.org/0000-0001-7374-8798)
- Junhao Wen (ORCID: https://orcid.org/0000-0003-2077-3070)
- Zhijian Yang (ORCID: https://orcid.org/0000-0002-7863-827X)
- Cassandra M Joynes
Institutions
- University of Southern California (US)
- National Institutes of Health (US)
- The University of Queensland (AU)
- The University of Melbourne (AU)
- Bellevue Hospital Center (US)
- National Institute on Aging (US)
- Center for Innovation (US)
- New York Genome Center (US)
- Artificial Intelligence in Medicine (Canada) (CA)
- Imperial College London (GB)
- Columbia University (US)
Publication Details
- Journal
- Nature Biomedical Engineering
- Published
- 2025-09-30
- DOI
- https://doi.org/10.1038/s41551-025-01506-5
- Citations
- 4
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 7.27