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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年9月30日

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  • Andrew Zalesky,
  • Ye Ella 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

摘要

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.