| Title: |
Associations between epilepsy-related polygenic risk and brain morphology in childhood |
| Authors: |
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; Bernhardt, Boris C; ENIGMA Consortium Epilepsy Working Group |
| Contributors: |
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; Bernhardt, Boris C; ENIGMA Consortium Epilepsy Working Group |
| Publication Year: |
2025 |
| Collection: |
Georg-August-Universität Göttingen: GoeScholar |
| 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 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, ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/brain/awaf259 |
| Availability: |
https://resolver.sub.uni-goettingen.de/purl?gro-2/150888; https://doi.org/10.1093/brain/awaf259 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.54230A77 |
| Database: |
BASE |