| Title: |
Associations between epilepsy-related polygenic risk and brain morphology in childhood |
| Authors: |
Ngo, Alexander; Liu, Lang; 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; Larivière, Sara; Bonilha, Leonardo; Gleichgerrcht, Ezequiel; Focke, Niels K; Kotikalapudi, Raviteja; O’Brien, Terence J; Sinclair, Benjamin; Vivash, Lucy; Desmond, Patricia M; Lui, Elaine; Vaudano, Anna Elisabetta; Kebets, Valeria; 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; Fett, Serena; Bauer, Tobias; Devinsky, Orrin; Striano, Pasquale; Kaestner, Erik; Caciagli, Lorenzo; Hatton, Sean N; Kirschner, Matthias; Duncan, John S; Thompson, Paul M; Abela, Eugenio; Weber, Clara F; Absil, Julie; Alhusaini, Saud; Carr, Sarah J A; Cavalleri, Gianpiero L; Davoodi-Bojd, Esmaeil; Delanty, Norman; Depondt, Chantal; Doherty, Colin P; Domin, Martin; Foley, Sonya; Royer, Jessica; Griffin, Aoife; Jackson, Graeme D; Kowalczyk, Magdalena; Labate, Angelo; Langner, Soenke; Mascalchi, Mario; Martin, Pascal; Richardson, Mark P; Rummel, Christian; Semmelroch, Mira; Yu, Eric; Severino, Mariasavina; Singh, Aditi; Thomas, Rhys H; Tondelli, Manuela; Tortora, Domenico; von Podewills, Felix; Vos, Sjoerd B; Whelan, Christopher D; Wiest, Roland; Zhang, Junsong; Rodríguez-Cruces, Raúl; McDonald, Carrie R; Sisodiya, Sanjay M; Bernasconi, Neda; Bernasconi, Andrea; Gan-Or, Ziv; Bernhardt, Boris C; Zhang, Zhiqiang |
| Source: |
Brain 149(2), 519–533 (2026). doi:10.1093/brain/awaf259 |
| Publisher Information: |
Oxford Univ. Press |
| Publication Year: |
2026 |
| Collection: |
Forschungszentrum Jülich: JuSER (Juelich Shared Electronic Resources) |
| Subject Terms: |
info:eu-repo/classification/ddc/610 |
| Subject Geographic: |
DE |
| Description: |
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 ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
1460-2156; 0006-8950 |
| Relation: |
info:eu-repo/semantics/altIdentifier/issn/1460-2156; info:eu-repo/semantics/altIdentifier/issn/0006-8950 |
| Availability: |
https://juser.fz-juelich.de/record/1052164; https://juser.fz-juelich.de/search?p=id:%22FZJ-2026-00802%22 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.B0696FFE |
| Database: |
BASE |