Integrating rare and common variation in epilepsy genetics: from genetic architecture to penetrance and clinical expressivity.

Integrating rare and common genetic variants reveals shared pathways influencing epilepsy severity and penetrance beyond traditional models.

• Why it matters: Current models separate rare high-effect variants from common small-effect variants, but they fail to explain variability in clinical outcomes and incomplete penetrance in epilepsy.
• What they did: The study reviews evidence from exome sequencing, CNV, and GWAS data across epilepsy subtypes, highlighting how rare and common variants may converge on shared genes and neurobiological processes.
• The result: Findings suggest that polygenic background and modifiers influence clinical expressivity and penetrance, informing future approaches in diagnosis, counseling, and personalized treatment, though models need further validation.