Associations between epilepsy-related polygenic risk and brain morphology in childhood

作者：Alexander Ngo, Lang Liu, Sara Larivière, Valeria Kebets, Serena Fett, Clara F. Weber, Jessica Royer, Eric Yu, Raúl Rodríguez‐Cruces, Zhiqiang Zhang, Leon Qi Rong Ooi, B.T. Thomas Yeo, Birgit Frauscher, Casey Paquola, Maria Eugenia Caligiuri, Antonio Gambardella, Luis Concha, Simon S. Keller, Fernando Cendes, Clarissa Lin Yasuda, Leonardo Bonilha, Ezequiel Gleichgerrcht, Niels K. Focke, Raviteja Kotikalapudi, Terence J. O’Brien, Benjamin Sinclair, Lucy Vivash, Patricia Desmond, Elaine Lui, Anna Elisabetta Vaudano, Stefano Meletti, Reetta Kälviäinen, Hamid Soltanian‐Zadeh, Gavin P. Winston, Vijay Tiwari, Barbara A. K. Kreilkamp, Matteo Lenge, Renzo Guerrini, Khalid Hamandi, Theodor Rüber, Tobias Bauer, Orrin Devinsky, Pasquale Striano, Erik Kaestner, Sean N. Hatton, Lorenzo Caciagli, Matthias Kirschner, John S. Duncan, Paul M. Thompson, Eugenio Abela, Julie Absil, Saud Alhusaini, Sarah J A Carr, Gianpiero L. Cavalleri, Esmaeil Davoodi‐Bojd, Norman Delanty, Chantal Depondt, Colin P. Doherty, Martin Domín, Sonya Foley, Aoife Griffin, Graeme D. Jackson, Magdalena Kowalczyk, Angelo Labate, Sönke Langner, Mario Mascalchi, Pascal Martin, Mark P. Richardson, Christian Rummel, Mira Semmelroch, Mariasavina Severino, Aditi Singh, Rhys H. Thomas, Manuela Tondelli, Domenico Tortora, Felix von Podewills, Sjoerd B. Vos, Christopher D. Whelan, Roland Wiest, Junsong Zhang, Carrie R. McDonald, Sanjay M. Sisodiya, Neda Bernasconi, Andrea Bernasconi, Ziv Gan‐Or, Boris C. Bernhardt · 发表于：Brain · 年份：2025 · DOI：10.1093/brain/awaf259 · 被引用次数：4 · 研究领域：Functional Brain Connectivity Studies、Advanced MRI Techniques and Applications、Epilepsy research and treatment

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 ...