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

Area of Science:

• Integrative biology and systems medicine.
• Human genetics and multi-omics research.

Background:

• Understanding interconnections among human organ systems is crucial for aging and disease research.
• Large-scale biobanks provide rich data for multi-organ investigations.

Purpose of the Study:

• To delineate a brain-heart-eye axis using multi-organ imaging, genetics, and proteomics data.
• To identify cross-organ phenotypic and genetic associations and causal relationships.
• To explore potential drug repurposing for multi-organ diseases.

Main Methods:

• Utilized multi-organ imaging (N=105,433), genetics, and proteomics (N=53,940) from UK Biobank, BALSA, FinnGen, and PGC.
• Analyzed brain patterns of structural covariance (PSC), heart imaging-derived phenotypes (IDPs), and eye IDPs.
• Performed proteome-wide associations, genetic parameter evaluation, and causal analyses.

Main Results:

• Identified the central autonomic network (brain-heart) and central visual pathway (brain-eye).
• Revealed within-organ specificity and cross-organ interconnections in proteomic associations.
• Demonstrated pleiotropic genetic effects across organs and cross-organ causal links to chronic diseases.

Conclusions:

• The study successfully mapped a detailed brain-heart-eye axis.
• Findings highlight potential for drug repurposing and improved prediction of systemic diseases.
• Provides a framework for multi-scale modeling of human aging and disease.