%0 Journal Article
%A Ngo, Alexander
%A Liu, Lang
%A Larivière, Sara
%A Kebets, Valeria
%A Fett, Serena
%A Weber, Clara F
%A Royer, Jessica
%A Yu, Eric
%A Rodríguez-Cruces, Raúl
%A Zhang, Zhiqiang
%A Ooi, Leon Qi Rong
%A Yeo, B T Thomas
%A Frauscher, Birgit
%A Paquola, Casey
%A Caligiuri, Maria Eugenia
%A Gambardella, Antonio
%A Concha, Luis
%A Keller, Simon S
%A Cendes, Fernando
%A Yasuda, Clarissa L
%A Bonilha, Leonardo
%A Gleichgerrcht, Ezequiel
%A Focke, Niels K N
%A Kotikalapudi, Raviteja
%A O'Brien, Terence J
%A Sinclair, Benjamin
%A Vivash, Lucy
%A Desmond, Patricia M
%A Lui, Elaine
%A Vaudano, Anna Elisabetta
%A Meletti, Stefano
%A Kälviäinen, Reetta
%A Soltanian-Zadeh, Hamid
%A Winston, Gavin P
%A Tiwari, Vijay K
%A Kreilkamp, Barbara A K
%A Lenge, Matteo
%A Guerrini, Renzo
%A Hamandi, Khalid
%A Rüber, Theodor
%A Bauer, Tobias
%A Devinsky, Orrin
%A Striano, Pasquale
%A Kaestner, Erik
%A Hatton, Sean N
%A Caciagli, Lorenzo
%A Kirschner, Matthias
%A Duncan, John S
%A Thompson, Paul M
%A McDonald, Carrie R
%A Sisodiya, Sanjay M
%A Bernasconi, Neda
%A Bernasconi, Andrea
%A Gan-Or, Ziv
%A Bernhardt, Boris C
%T Associations between epilepsy-related polygenic risk and brain morphology in childhood.
%J Brain
%V 149
%N 2
%@ 0006-8950
%C Oxford
%I Oxford Univ. Press
%M DZNE-2026-00165
%P 519 - 533
%D 2026
%X 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.
%K Humans
%K Male
%K Female
%K Child
%K Adolescent
%K Multifactorial Inheritance: genetics
%K Magnetic Resonance Imaging
%K Brain: pathology
%K Brain: diagnostic imaging
%K Epilepsy, Temporal Lobe: genetics
%K Epilepsy, Temporal Lobe: pathology
%K Epilepsy, Temporal Lobe: diagnostic imaging
%K Atrophy
%K Genetic Predisposition to Disease
%K Genome-Wide Association Study
%K Hippocampus: pathology
%K Hippocampus: diagnostic imaging
%K Epilepsy: genetics
%K Epilepsy: pathology
%K Epilepsy: diagnostic imaging
%K Case-Control Studies
%K Sclerosis: pathology
%K Risk Factors
%K brain structure (Other)
%K childhood (Other)
%K genetic risk (Other)
%K imaging-genetics (Other)
%K temporal lobe epilepsy (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40811581
%R 10.1093/brain/awaf259
%U https://pub.dzne.de/record/285041