Shared Immunogenetic Basis Between Spleen Volume and Psychiatric Disorders

Area of Science:

• Neuroimmunology
• Psychiatric Genetics
• Systems Biology

Background:

• Psychiatric disorders are linked to immune system dysfunction.
• The genetic relationship between the spleen and psychiatric disorders is not well understood.
• Understanding the spleen-brain axis is crucial for psychiatric research.

Purpose of the Study:

• To investigate the genetic correlations between spleen volume and major psychiatric disorders (schizophrenia, bipolar disorder, depression).
• To identify shared genes and biological pathways between spleen volume and depression.
• To explore the cellular and functional genomic underpinnings of the spleen-brain connection in depression.

Main Methods:

• Linkage Disequilibrium Score Regression (LDSC) for genetic correlation analysis.
• MAGMA gene-level analysis and pathway enrichment (KEGG, GO) for shared genes.
• Protein-protein interaction (PPI) network analysis and single-cell transcriptomic analysis.
• Transcriptome-Wide Association Study (TWAS) in brain regions.

Main Results:

• Significant genetic correlation found only between spleen volume and depression.
• Identified 25 shared genes enriched in immune/inflammatory pathways (e.g., antigen processing, NF-κB signaling).
• Microglia identified as a key cell type; TWAS revealed enrichment in immune, neurotransmitter, and metabolic pathways.

Conclusions:

• Depression and spleen volume share an immunoinflammatory genetic basis.
• The spleen-brain axis in depression may involve microglia-mediated immune mechanisms.
• Provides novel genetic evidence for the spleen-brain interaction in the context of depression.