TY  - JOUR
AU  - Ngo, Alexander
AU  - Liu, Lang
AU  - Larivière, Sara
AU  - Kebets, Valeria
AU  - Fett, Serena
AU  - Weber, Clara F
AU  - Royer, Jessica
AU  - Yu, Eric
AU  - Rodríguez-Cruces, Raúl
AU  - Zhang, Zhiqiang
AU  - Ooi, Leon Qi Rong
AU  - Yeo, B T Thomas
AU  - Frauscher, Birgit
AU  - Paquola, Casey
AU  - Caligiuri, Maria Eugenia
AU  - Gambardella, Antonio
AU  - Concha, Luis
AU  - Keller, Simon S
AU  - Cendes, Fernando
AU  - Yasuda, Clarissa L
AU  - Bonilha, Leonardo
AU  - Gleichgerrcht, Ezequiel
AU  - Focke, Niels K N
AU  - Kotikalapudi, Raviteja
AU  - O'Brien, Terence J
AU  - Sinclair, Benjamin
AU  - Vivash, Lucy
AU  - Desmond, Patricia M
AU  - Lui, Elaine
AU  - Vaudano, Anna Elisabetta
AU  - Meletti, Stefano
AU  - Kälviäinen, Reetta
AU  - Soltanian-Zadeh, Hamid
AU  - Winston, Gavin P
AU  - Tiwari, Vijay K
AU  - Kreilkamp, Barbara A K
AU  - Lenge, Matteo
AU  - Guerrini, Renzo
AU  - Hamandi, Khalid
AU  - Rüber, Theodor
AU  - Bauer, Tobias
AU  - Devinsky, Orrin
AU  - Striano, Pasquale
AU  - Kaestner, Erik
AU  - Hatton, Sean N
AU  - Caciagli, Lorenzo
AU  - Kirschner, Matthias
AU  - Duncan, John S
AU  - Thompson, Paul M
AU  - McDonald, Carrie R
AU  - Sisodiya, Sanjay M
AU  - Bernasconi, Neda
AU  - Bernasconi, Andrea
AU  - Gan-Or, Ziv
AU  - Bernhardt, Boris C
TI  - Associations between epilepsy-related polygenic risk and brain morphology in childhood.
JO  - Brain
VL  - 149
IS  - 2
SN  - 0006-8950
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DZNE-2026-00165
SP  - 519 - 533
PY  - 2026
AB  - Extensive neuroimaging research in temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) has identified brain atrophy as a disease phenotype. While it is also related to a complex genetic architecture, the transition from genetic risk factors to brain vulnerabilities remains unclear. Using a population-based approach, we examined the associations between epilepsy-related polygenic risk for HS (PRS-HS) and brain structure in healthy developing children, assessed their relation to brain network architecture, and evaluated its correspondence with case-control findings in TLE-HS diagnosed patients relative to healthy individuals. We used genome-wide genotyping and structural T1-weighted MRI of 3826 neurotypical children from the Adolescent Brain Cognitive Development (ABCD) study. Surface-based linear models related PRS-HS to cortical thickness measures, and subsequently contextualized findings with structural and functional network architecture based on epicentre mapping approaches. Imaging-genetic associations were then correlated to atrophy and disease epicentres in 785 patients with TLE-HS relative to 1512 healthy controls aggregated across multiple sites. Higher PRS-HS was associated with decreases in cortical thickness across temporo-parietal as well as fronto-central regions of neurotypical children. These imaging-genetic effects were anchored to the connectivity profiles of distinct functional and structural epicentres. Compared with disease-related alterations from a separate epilepsy cohort, regional and network correlates of PRS-HS strongly mirrored cortical atrophy and disease epicentres observed in patients with TLE-HS and were highly replicable across different studies. Findings were consistent when using statistical models controlling for spatial autocorrelations and robust to variations in analytic methods. Capitalizing on recent imaging-genetic initiatives, our study provides novel insights into the genetic underpinnings of structural alterations in TLE-HS, revealing common morphological and network pathways between genetic vulnerability and disease mechanisms. These signatures offer a foundation for early risk stratification and personalized interventions targeting genetic profiles in epilepsy.
KW  - Humans
KW  - Male
KW  - Female
KW  - Child
KW  - Adolescent
KW  - Multifactorial Inheritance: genetics
KW  - Magnetic Resonance Imaging
KW  - Brain: pathology
KW  - Brain: diagnostic imaging
KW  - Epilepsy, Temporal Lobe: genetics
KW  - Epilepsy, Temporal Lobe: pathology
KW  - Epilepsy, Temporal Lobe: diagnostic imaging
KW  - Atrophy
KW  - Genetic Predisposition to Disease
KW  - Genome-Wide Association Study
KW  - Hippocampus: pathology
KW  - Hippocampus: diagnostic imaging
KW  - Epilepsy: genetics
KW  - Epilepsy: pathology
KW  - Epilepsy: diagnostic imaging
KW  - Case-Control Studies
KW  - Sclerosis: pathology
KW  - Risk Factors
KW  - brain structure (Other)
KW  - childhood (Other)
KW  - genetic risk (Other)
KW  - imaging-genetics (Other)
KW  - temporal lobe epilepsy (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40811581
DO  - DOI:10.1093/brain/awaf259
UR  - https://pub.dzne.de/record/285041
ER  -