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

Ngo, A.; Liu, L.; Lariviere, S.; Kebets, V.; Fett, S.; Weber, C. F.; Royer, J.; Yu, E.; Rodriguez-Cruces, R.; Zhang, Z.; Ooi, L. Q. R.; Yeo, B. T. T.; Frauscher, B.; Paquola, C.; Caligiuri, M. E.; Gambardella, A.; Concha, L.; Keller, S. S.; Cendes, F.; Yasuda, C. L.; Bonilha, L.; Gleichgerrcht, E.; Focke, N. K.; Kotikalapudi, R.; O'Brien, T. J.; Sinclair, B.; Vivash, L.; Desmond, P. M.; Lui, E.; Vaudano, A. E.; Meletti, S.; Kälviäinwn, R.; Soltanian-Zadeh, H.; Winston, G. P.; Tiwari, V. K.; Kreilkamp, B. A. K.; Lenge, M.; Guerrini, R.; Hamandi, K.; Rüber, T.; Bauer, T.; Devinsky, O.; Strian

doi:10.1101/2025.01.17.633277

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bioRxiv · 10.1101/2025.01.17.633277

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

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Abstract

AO_SCPLOWBSTRACTC_SCPLOWTemporal 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.

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Ngo, A., Liu, L., Lariviere, S., Kebets, V., Fett, S., Weber, C. F., Royer, J., Yu, E., Rodriguez-Cruces, R., Zhang, Z., Ooi, L. Q. R., Yeo, B. T. T., Frauscher, B., Paquola, C., Caligiuri, M. E., Gambardella, A., Concha, L., Keller, S. S., Cendes, F., Yasuda, C. L., Bonilha, L., Gleichgerrcht, E., Focke, N. K., Kotikalapudi, R., O'Brien, T. J., Sinclair, B., Vivash, L., Desmond, P. M., Lui, E., Vaudano, A. E., Meletti, S., Kälviäinwn, R., Soltanian-Zadeh, H., Winston, G. P., Tiwari, V. K., Kreilkamp, B. A. K., Lenge, M., Guerrini, R., Hamandi, K., Rüber, T., Bauer, T., Devinsky, O., Strian. 2025-01-17. Associations between epilepsy-related polygenic risk and brain morphology in childhood. https://doi.org/10.1101/2025.01.17.633277

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