Associations between epilepsy-related polygenic risk and brain morphology in childhood.
Publisher DOI
PubMed ID
40811581
Abstract
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 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.
Date Issued
2026-02-07
Publication Type
Article
Subject(s)
Subjects
brain structure
•
childhood
•
genetic risk
•
imaging-genetics
•
temporal lobe epilepsy
Language(s)
en
Author(s)
Ngo, Alexander | |
Liu, Lang | |
Larivière, Sara | |
Kebets, Valeria | |
Fett, Serena | |
Weber, Clara F | |
Royer, Jessica | |
Yu, Eric | |
Rodríguez-Cruces, Raúl | |
Zhang, Zhiqiang | |
Ooi, Leon Qi Rong | |
Yeo, B T Thomas | |
Frauscher, Birgit | |
Paquola, Casey | |
Caligiuri, Maria Eugenia | |
Gambardella, Antonio | |
Concha, Luis | |
Keller, Simon S | |
Cendes, Fernando | |
Yasuda, Clarissa L | |
Bonilha, Leonardo | |
Gleichgerrcht, Ezequiel | |
Focke, Niels K | |
O'Brien, Terence J | |
Sinclair, Benjamin | |
Vivash, Lucy | |
Desmond, Patricia M | |
Lui, Elaine | |
Vaudano, Anna Elisabetta | |
Meletti, Stefano | |
Kälviäinen, Reetta | |
Soltanian-Zadeh, Hamid | |
Winston, Gavin P | |
Tiwari, Vijay K | |
Kreilkamp, Barbara A K | |
Lenge, Matteo | |
Guerrini, Renzo | |
Hamandi, Khalid | |
Rüber, Theodor | |
Bauer, Tobias | |
Devinsky, Orrin | |
Striano, Pasquale | |
Kaestner, Erik | |
Hatton, Sean N | |
Kirschner, Matthias | |
Duncan, John S | |
Thompson, Paul M | |
McDonald, Carrie R | |
Sisodiya, Sanjay M | |
Bernasconi, Neda | |
Bernasconi, Andrea | |
Gan-Or, Ziv | |
Bernhardt, Boris C |
Additional Credits
Journal
Brain
Publisher
Oxford University Press
ISSN
1460-2156
0006-8950
Access(Rights)
open.access