ASSOCIATIONS BETWEEN EPILEPSY-RELATED POLYGENIC RISK AND BRAIN MORPHOLOGY IN CHILDHOOD

Area of Science:

• Neuroscience
• Genetics
• Medical Imaging

Background:

• Temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) has a complex genetic basis, but the link between genetic risk and brain changes is not fully understood.
• Understanding this connection is crucial for identifying individuals at risk and developing targeted interventions.

Purpose of the Study:

• To investigate the association between polygenic risk scores for HS (PRS-HS) and brain structure in neurotypical children.
• To compare these structural signatures with findings in TLE-HS patients to identify shared disease mechanisms.

Main Methods:

• Utilized imaging-genetic analyses in a large cohort of neurotypical children.
• Correlated PRS-HS with brain structure, specifically cortical thickness.
• Compared findings with multicentric case-control data from TLE-HS patients.

Main Results:

• Identified PRS-HS-related cortical thinning in temporo-parietal and fronto-central regions in neurotypical children.
• These structural changes were linked to specific functional and structural network hubs.
• Observed that PRS-HS structural correlates mirrored atrophy and network patterns in TLE-HS patients.

Conclusions:

• Findings suggest a potential pathway from genetic vulnerability to brain structural alterations in TLE-HS.
• Highlights the utility of imaging-genetic biomarkers for early risk stratification and personalized interventions in TLE-HS.