Candidate risk genes for bipolar disorder are highly conserved during evolution and highly interconnected

Area of Science:

• Genetics
• Evolutionary Biology
• Psychiatric Disorders

Background:

• Bipolar disorder (BPD) is a complex, highly heritable psychiatric condition with poorly understood genetic underpinnings.
• Previous studies have identified candidate risk genes for BPD, but their broader biological roles require further characterization.

Purpose of the Study:

• To investigate the evolutionary conservation, associated phenotypes, and gene-gene interactions of BPD risk genes.
• To identify potential molecular pathways and comorbidities linked to BPD through genetic analysis.

Main Methods:

• Homologous genes of human BPD risk genes were identified in model organisms (C. elegans, zebrafish, Drosophila) using database searches and BLAST.
• Phenotypes of C. elegans genes were annotated. Gene-gene interactions were quantified using GeneMANIA, comparing BPD risk genes to random gene sets.

Main Results:

• BPD risk genes exhibit high evolutionary conservation and are enriched for essential and lethality-associated genes.
• These genes are significantly more interconnected than random gene sets, with identified syntenic blocks suggesting links to comorbidities like coronary disease and obesity.
• Associated phenotypes extend beyond neurological functions, including altered lifespan.

Conclusions:

• BPD risk genes possess unique characteristics regarding conservation, interconnectedness, and pleiotropic effects impacting multiple biological systems.
• Key regulatory genes within these networks may serve as promising targets for novel therapeutic strategies for BPD.