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001052164 1001_ $$0P:(DE-HGF)0$$aNgo, Alexander$$b0
001052164 245__ $$aAssociations between epilepsy-related polygenic risk and brain morphology in childhood
001052164 260__ $$aOxford$$bOxford Univ. Press$$c2025
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001052164 520__ $$aExtensive 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 common morphological and network pathways between genetic vulnerability and disease mechanisms. These signatures offer a foundation for early risk stratification and personalized interventions targeting genetic profiles in epilepsy.
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001052164 7001_ $$0P:(DE-HGF)0$$aLiu, Lang$$b1
001052164 7001_ $$0P:(DE-HGF)0$$aLarivière, Sara$$b2
001052164 7001_ $$0P:(DE-HGF)0$$aKebets, Valeria$$b3
001052164 7001_ $$0P:(DE-HGF)0$$aFett, Serena$$b4
001052164 7001_ $$0P:(DE-HGF)0$$aWeber, Clara F$$b5
001052164 7001_ $$0P:(DE-HGF)0$$aRoyer, Jessica$$b6
001052164 7001_ $$0P:(DE-HGF)0$$aYu, Eric$$b7
001052164 7001_ $$0P:(DE-HGF)0$$aRodríguez-Cruces, Raúl$$b8
001052164 7001_ $$0P:(DE-HGF)0$$aZhang, Zhiqiang$$b9
001052164 7001_ $$0P:(DE-HGF)0$$aOoi, Leon Qi Rong$$b10
001052164 7001_ $$0P:(DE-HGF)0$$aYeo, B T Thomas$$b11
001052164 7001_ $$0P:(DE-HGF)0$$aFrauscher, Birgit$$b12
001052164 7001_ $$0P:(DE-Juel1)187055$$aPaquola, Casey$$b13
001052164 7001_ $$0P:(DE-HGF)0$$aCaligiuri, Maria Eugenia$$b14
001052164 7001_ $$00000-0001-7384-3074$$aGambardella, Antonio$$b15
001052164 7001_ $$00000-0002-7842-3869$$aConcha, Luis$$b16
001052164 7001_ $$0P:(DE-HGF)0$$aKeller, Simon S$$b17
001052164 7001_ $$0P:(DE-HGF)0$$aCendes, Fernando$$b18
001052164 7001_ $$0P:(DE-HGF)0$$aYasuda, Clarissa L$$b19
001052164 7001_ $$0P:(DE-HGF)0$$aBonilha, Leonardo$$b20
001052164 7001_ $$0P:(DE-HGF)0$$aGleichgerrcht, Ezequiel$$b21
001052164 7001_ $$0P:(DE-HGF)0$$aFocke, Niels K$$b22
001052164 7001_ $$0P:(DE-HGF)0$$aKotikalapudi, Raviteja$$b23
001052164 7001_ $$0P:(DE-HGF)0$$aO’Brien, Terence J$$b24
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001052164 7001_ $$00000-0002-6280-7526$$aVaudano, Anna Elisabetta$$b29
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001052164 7001_ $$00000-0003-0044-4632$$aDevinsky, Orrin$$b41
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001052164 7001_ $$0P:(DE-HGF)0$$aKaestner, Erik$$b43
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001052164 7001_ $$00000-0002-9149-8726$$aHatton, Sean N$$b45
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001052164 7001_ $$0P:(DE-HGF)0$$aDoherty, Colin P$$b57
001052164 7001_ $$0P:(DE-HGF)0$$aDomin, Martin$$b58
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001052164 7001_ $$00000-0001-8925-3140$$aRichardson, Mark P$$b67
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001052164 7001_ $$00000-0003-4730-5322$$aSeverino, Mariasavina$$b70
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001052164 7001_ $$0P:(DE-HGF)0$$aThomas, Rhys H$$b72
001052164 7001_ $$0P:(DE-HGF)0$$aTondelli, Manuela$$b73
001052164 7001_ $$00000-0002-5621-4046$$aTortora, Domenico$$b74
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001052164 7001_ $$0P:(DE-HGF)0$$aVos, Sjoerd B$$b76
001052164 7001_ $$0P:(DE-HGF)0$$aWhelan, Christopher D$$b77
001052164 7001_ $$0P:(DE-HGF)0$$aWiest, Roland$$b78
001052164 7001_ $$0P:(DE-HGF)0$$aZhang, Junsong$$b79
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001052164 7001_ $$0P:(DE-HGF)0$$aBernhardt, Boris C$$b85$$eCorresponding author
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