ASSOCIATIONS BETWEEN EPILEPSY-RELATED POLYGENIC RISK AND BRAIN MORPHOLOGY IN CHILDHOOD.

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Ngo, Alexander ORCID: 0000-0002-8999-9388, Liu, Lang ORCID: 0000-0002-0348-2258, Larivière, Sara ORCID: 0000-0001-5701-1307, Kebets, Valeria ORCID: 0000-0003-1707-7437, Fett, Serena, Weber, Clara F ORCID: 0000-0002-0836-8833, Royer, Jessica ORCID: 0000-0002-4448-8998, Yu, Eric ORCID: 0000-0003-3525-4564, Rodríguez-Cruces, Raúl ORCID: 0000-0002-2917-1212, Zhang, Zhiqiang ORCID: 0000-0002-3993-7330 et al (show 46 more authors) , Ooi, Leon Qi Rong ORCID: 0000-0002-3546-4580, Thomas Yeo, BT ORCID: 0000-0002-0119-3276, Frauscher, Birgit ORCID: 0000-0001-6064-1529, Paquola, Casey ORCID: 0000-0002-0190-4103, Caligiuri, Maria Eugenia ORCID: 0000-0002-2030-5552, Gambardella, Antonio ORCID: 0000-0001-7384-3074, Concha, Luis ORCID: 0000-0002-7842-3869, Keller, Simon S ORCID: 0000-0001-5247-9795, Cendes, Fernando ORCID: 0000-0001-9336-9568, Yasuda, Clarissa L ORCID: 0000-0001-9084-7173, Bonilha, Leonardo ORCID: 0000-0002-6153-8942, Gleichgerrcht, Ezequiel ORCID: 0000-0002-4212-4146, Focke, Niels K ORCID: 0000-0001-5486-6289, Kotikalapudi, Raviteja ORCID: 0000-0003-4604-3367, O'Brien, Terence J ORCID: 0000-0002-7198-8621, Sinclair, Benjamin ORCID: 0009-0007-3009-3761, Vivash, Lucy ORCID: 0000-0002-1182-0907, Desmond, Patricia M ORCID: 0000-0002-4803-6323, Lui, Elaine, Vaudano, Anna Elisabetta ORCID: 0000-0002-6280-7526, Meletti, Stefano ORCID: 0000-0003-0334-539X, Kälviäinen, Reetta, Soltanian-Zadeh, Hamid ORCID: 0000-0002-7302-6856, Winston, Gavin P ORCID: 0000-0001-9395-1478, Tiwari, Vijay K ORCID: 0000-0003-0292-6635, Kreilkamp, Barbara AK ORCID: 0000-0001-6881-5191, Lenge, Matteo ORCID: 0000-0003-2848-621X, Guerrini, Renzo ORCID: 0000-0002-7272-7079, Hamandi, Khalid ORCID: 0000-0001-7116-262X, Rüber, Theodor ORCID: 0000-0002-6180-7671, Bauer, Tobias ORCID: 0000-0002-0555-6214, Devinsky, Orrin ORCID: 0000-0003-0044-4632, Striano, Pasquale ORCID: 0000-0002-6065-1476, Kaestner, Erik ORCID: 0000-0003-3252-5365, Hatton, Sean N ORCID: 0000-0002-9149-8726, Caciagli, Lorenzo ORCID: 0000-0001-7189-9699, Kirschner, Matthias ORCID: 0000-0002-9486-1439, Duncan, John S ORCID: 0000-0002-1373-0681, Thompson, Paul M ORCID: 0000-0002-4720-8867, ENIGMA Consortium Epilepsy Working Group, McDonald, Carrie R, Sisodiya, Sanjay M ORCID: 0000-0002-1511-5893, Bernasconi, Neda, Bernasconi, Andrea, Gan-Or, Ziv ORCID: 0000-0003-0332-234X and Bernhardt, Boris C ORCID: 0000-0001-9256-6041 (2025) ASSOCIATIONS BETWEEN EPILEPSY-RELATED POLYGENIC RISK AND BRAIN MORPHOLOGY IN CHILDHOOD. [Preprint]

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Abstract

Temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) is associated with a complex genetic architecture, but the translation from genetic risk factors to brain vulnerability remains unclear. Here, we examined associations between epilepsy-related polygenic risk scores for HS (PRS-HS) and brain structure in a large sample of neurotypical children, and correlated these signatures with case-control findings in in multicentric cohorts of patients with TLE-HS. Imaging-genetic analyses revealed PRS-related cortical thinning in temporo-parietal and fronto-central regions, strongly anchored to distinct functional and structural network epicentres. Compared to disease-related effects derived from epilepsy case-control cohorts, structural correlates of PRS-HS mirrored atrophy and epicentre patterns in patients with TLE-HS. By identifying a potential pathway between genetic vulnerability and disease mechanisms, our findings provide new insights into the genetic underpinnings of structural alterations in TLE-HS and highlight potential imaging-genetic biomarkers for early risk stratification and personalized interventions.

Item Type:	Preprint
Uncontrolled Keywords:	Imaging-genetics, brain structure, childhood, genetic risk, temporal lobe epilepsy
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	29 Jan 2025 15:36
Last Modified:	23 May 2026 09:44
DOI:	10.1101/2025.01.17.633277
Open Access URL:	https://www.biorxiv.org/content/10.1101/2025.01.17...
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3189994
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