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000285041 1001_ $$00000-0002-8999-9388$$aNgo, Alexander$$b0
000285041 245__ $$aAssociations between epilepsy-related polygenic risk and brain morphology in childhood.
000285041 260__ $$aOxford$$bOxford Univ. Press$$c2026
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000285041 520__ $$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 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 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 were 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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000285041 650_7 $$2Other$$abrain structure
000285041 650_7 $$2Other$$achildhood
000285041 650_7 $$2Other$$agenetic risk
000285041 650_7 $$2Other$$aimaging-genetics
000285041 650_7 $$2Other$$atemporal lobe epilepsy
000285041 650_2 $$2MeSH$$aHumans
000285041 650_2 $$2MeSH$$aMale
000285041 650_2 $$2MeSH$$aFemale
000285041 650_2 $$2MeSH$$aChild
000285041 650_2 $$2MeSH$$aAdolescent
000285041 650_2 $$2MeSH$$aMultifactorial Inheritance: genetics
000285041 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000285041 650_2 $$2MeSH$$aBrain: pathology
000285041 650_2 $$2MeSH$$aBrain: diagnostic imaging
000285041 650_2 $$2MeSH$$aEpilepsy, Temporal Lobe: genetics
000285041 650_2 $$2MeSH$$aEpilepsy, Temporal Lobe: pathology
000285041 650_2 $$2MeSH$$aEpilepsy, Temporal Lobe: diagnostic imaging
000285041 650_2 $$2MeSH$$aAtrophy
000285041 650_2 $$2MeSH$$aGenetic Predisposition to Disease
000285041 650_2 $$2MeSH$$aGenome-Wide Association Study
000285041 650_2 $$2MeSH$$aHippocampus: pathology
000285041 650_2 $$2MeSH$$aHippocampus: diagnostic imaging
000285041 650_2 $$2MeSH$$aEpilepsy: genetics
000285041 650_2 $$2MeSH$$aEpilepsy: pathology
000285041 650_2 $$2MeSH$$aEpilepsy: diagnostic imaging
000285041 650_2 $$2MeSH$$aCase-Control Studies
000285041 650_2 $$2MeSH$$aSclerosis: pathology
000285041 650_2 $$2MeSH$$aRisk Factors
000285041 7001_ $$aLiu, Lang$$b1
000285041 7001_ $$aLarivière, Sara$$b2
000285041 7001_ $$aKebets, Valeria$$b3
000285041 7001_ $$aFett, Serena$$b4
000285041 7001_ $$aWeber, Clara F$$b5
000285041 7001_ $$00000-0002-4448-8998$$aRoyer, Jessica$$b6
000285041 7001_ $$aYu, Eric$$b7
000285041 7001_ $$aRodríguez-Cruces, Raúl$$b8
000285041 7001_ $$aZhang, Zhiqiang$$b9
000285041 7001_ $$aOoi, Leon Qi Rong$$b10
000285041 7001_ $$aYeo, B T Thomas$$b11
000285041 7001_ $$aFrauscher, Birgit$$b12
000285041 7001_ $$aPaquola, Casey$$b13
000285041 7001_ $$aCaligiuri, Maria Eugenia$$b14
000285041 7001_ $$00000-0001-7384-3074$$aGambardella, Antonio$$b15
000285041 7001_ $$00000-0002-7842-3869$$aConcha, Luis$$b16
000285041 7001_ $$aKeller, Simon S$$b17
000285041 7001_ $$aCendes, Fernando$$b18
000285041 7001_ $$aYasuda, Clarissa L$$b19
000285041 7001_ $$aBonilha, Leonardo$$b20
000285041 7001_ $$aGleichgerrcht, Ezequiel$$b21
000285041 7001_ $$00000-0001-5486-6289$$aFocke, Niels K N$$b22
000285041 7001_ $$aKotikalapudi, Raviteja$$b23
000285041 7001_ $$aO'Brien, Terence J$$b24
000285041 7001_ $$aSinclair, Benjamin$$b25
000285041 7001_ $$00000-0002-1182-0907$$aVivash, Lucy$$b26
000285041 7001_ $$aDesmond, Patricia M$$b27
000285041 7001_ $$aLui, Elaine$$b28
000285041 7001_ $$00000-0002-6280-7526$$aVaudano, Anna Elisabetta$$b29
000285041 7001_ $$00000-0003-0334-539X$$aMeletti, Stefano$$b30
000285041 7001_ $$aKälviäinen, Reetta$$b31
000285041 7001_ $$aSoltanian-Zadeh, Hamid$$b32
000285041 7001_ $$aWinston, Gavin P$$b33
000285041 7001_ $$aTiwari, Vijay K$$b34
000285041 7001_ $$aKreilkamp, Barbara A K$$b35
000285041 7001_ $$00000-0003-2848-621X$$aLenge, Matteo$$b36
000285041 7001_ $$aGuerrini, Renzo$$b37
000285041 7001_ $$aHamandi, Khalid$$b38
000285041 7001_ $$00000-0002-6180-7671$$aRüber, Theodor$$b39
000285041 7001_ $$0P:(DE-2719)9002598$$aBauer, Tobias$$b40
000285041 7001_ $$00000-0003-0044-4632$$aDevinsky, Orrin$$b41
000285041 7001_ $$00000-0002-6065-1476$$aStriano, Pasquale$$b42
000285041 7001_ $$aKaestner, Erik$$b43
000285041 7001_ $$00000-0002-9149-8726$$aHatton, Sean N$$b44
000285041 7001_ $$aCaciagli, Lorenzo$$b45
000285041 7001_ $$00000-0002-9486-1439$$aKirschner, Matthias$$b46
000285041 7001_ $$00000-0002-1373-0681$$aDuncan, John S$$b47
000285041 7001_ $$aThompson, Paul M$$b48
000285041 7001_ $$aGroup, ENIGMA Consortium Epilepsy Working$$b49$$eCollaboration Author
000285041 7001_ $$aMcDonald, Carrie R$$b50
000285041 7001_ $$00000-0002-1511-5893$$aSisodiya, Sanjay M$$b51
000285041 7001_ $$aBernasconi, Neda$$b52
000285041 7001_ $$00000-0001-9358-5703$$aBernasconi, Andrea$$b53
000285041 7001_ $$00000-0003-0332-234X$$aGan-Or, Ziv$$b54
000285041 7001_ $$aBernhardt, Boris C$$b55
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