%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
%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 Caciagli, Lorenzo
%A Hatton, Sean N
%A Kirschner, Matthias
%A Duncan, John S
%A Thompson, Paul M
%A Abela, Eugenio
%A Absil, Julie
%A Alhusaini, Saud
%A Carr, Sarah J A
%A Cavalleri, Gianpiero L
%A Davoodi-Bojd, Esmaeil
%A Delanty, Norman
%A Depondt, Chantal
%A Doherty, Colin P
%A Domin, Martin
%A Foley, Sonya
%A Griffin, Aoife
%A Jackson, Graeme D
%A Kowalczyk, Magdalena
%A Labate, Angelo
%A Langner, Soenke
%A Mascalchi, Mario
%A Martin, Pascal
%A Richardson, Mark P
%A Rummel, Christian
%A Semmelroch, Mira
%A Severino, Mariasavina
%A Singh, Aditi
%A Thomas, Rhys H
%A Tondelli, Manuela
%A Tortora, Domenico
%A von Podewills, Felix
%A Vos, Sjoerd B
%A Whelan, Christopher D
%A Wiest, Roland
%A Zhang, Junsong
%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 .
%@ 0006-8950
%C Oxford
%I Oxford Univ. Press
%M FZJ-2026-00802
%P awaf259
%D 2025
%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 individualsWe used genome-wide genotyping and structural T1-weighted magnetic resonance imaging (MRI) of 3,826 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 1,512 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 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%R 10.1093/brain/awaf259
%U https://juser.fz-juelich.de/record/1052164