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

Area of Science:

• Integrative biology
• Systems biology
• Genetics and omics

Background:

• Understanding human aging and disease mechanisms requires investigating interconnections among multiple organ systems.
• The MULTI Consortium consolidates multi-organ imaging, genetics, and proteomics data for comprehensive analysis.

Purpose of the Study:

• To delineate a brain-heart-eye axis using multi-organ data.
• To explore cross-organ genetic influences and causal relationships with chronic diseases.
• To assess the predictive power of integrated multi-organ and multi-omics features.

Main Methods:

• Utilized multi-organ imaging, individual- and summary-level genetics, and proteomics data.
• Analyzed brain patterns of structural covariance (PSCs), heart imaging-derived phenotypes (IDPs), and eye IDPs.
• Performed proteome-wide associations, genetic parameter estimation, gene-drug-disease network analysis, and causal inference.

Main Results:

• Identified within-organ specificity and cross-organ interconnections in proteome-wide associations.
• Observed pleiotropic effects of single-nucleotide polymorphisms across organs.
• Revealed cross-organ causal relationships between PSCs/IDPs and chronic diseases (e.g., Alzheimer's, heart failure, glaucoma).

Conclusions:

• The brain-heart-eye axis provides insights into aging and disease mechanisms.
• Integrating multi-organ and multi-omics data improves prediction of systemic diseases and cognition.
• Findings suggest potential for drug repurposing and novel therapeutic strategies for cross-organ conditions.