Brain–heart–eye axis revealed by multi-organ imaging genetics and proteomics

作者：Andrew Zalesky, Ye Tian, Luigi Ferrucci, Wenjia Bai, Michael S. Rafii, Paul Aisen, Jian Zeng, Aleix Boquet-Pujadas, Filippos Anagnostakis, Michael R. Duggan, Cassandra M Joynes, Arthur W. Toga, Zhijian Yang, Keenan A. Walker, Christos Davatzikos, Junhao Wen · 发表于：Nature Biomedical Engineering · 年份：2025 · DOI：10.1038/s41551-025-01506-5 · 被引用次数：9 · 研究领域：Genetic Associations and Epidemiology、Glaucoma and retinal disorders、Cardiovascular Disease and Adiposity

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.