Ngo, AlexanderAlexanderNgoLiu, LangLangLiuLarivière, SaraSaraLarivièreKebets, ValeriaValeriaKebetsFett, SerenaSerenaFettWeber, Clara FClara FWeberRoyer, JessicaJessicaRoyerYu, EricEricYuRodríguez-Cruces, RaúlRaúlRodríguez-CrucesZhang, ZhiqiangZhiqiangZhangOoi, Leon Qi RongLeon Qi RongOoiThomas Yeo, B TB TThomas YeoFrauscher, BirgitBirgitFrauscherPaquola, CaseyCaseyPaquolaCaligiuri, Maria EugeniaMaria EugeniaCaligiuriGambardella, AntonioAntonioGambardellaConcha, LuisLuisConchaKeller, Simon SSimon SKellerCendes, FernandoFernandoCendesYasuda, Clarissa LClarissa LYasudaBonilha, LeonardoLeonardoBonilhaGleichgerrcht, EzequielEzequielGleichgerrchtFocke, Niels KNiels KFockeKotikalapudi, RavitejaRavitejaKotikalapudiO'Brien, Terence JTerence JO'BrienSinclair, BenjaminBenjaminSinclairVivash, LucyLucyVivashDesmond, Patricia MPatricia MDesmondLui, ElaineElaineLuiVaudano, Anna ElisabettaAnna ElisabettaVaudanoMeletti, StefanoStefanoMelettiKälviäinen, ReettaReettaKälviäinenSoltanian-Zadeh, HamidHamidSoltanian-ZadehWinston, Gavin PGavin PWinstonTiwari, Vijay KVijay KTiwariKreilkamp, Barbara A KBarbara A KKreilkampLenge, MatteoMatteoLengeGuerrini, RenzoRenzoGuerriniHamandi, KhalidKhalidHamandiRüber, TheodorTheodorRüberBauer, TobiasTobiasBauerDevinsky, OrrinOrrinDevinskyStriano, PasqualePasqualeStrianoKaestner, ErikErikKaestnerHatton, Sean NSean NHattonCaciagli, LorenzoLorenzoCaciagliKirschner, MatthiasMatthiasKirschnerDuncan, John SJohn SDuncanThompson, Paul MPaul MThompsonMcDonald, Carrie RCarrie RMcDonaldSisodiya, Sanjay MSanjay MSisodiyaBernasconi, NedaNedaBernasconiBernasconi, AndreaAndreaBernasconiGan-Or, ZivZivGan-OrBernhardt, Boris CBoris CBernhardt2025-03-052025-03-052025-01-17https://boris-portal.unibe.ch/handle/20.500.12422/204595Temporal 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.enImaging-geneticsbrain structurechildhoodgenetic risktemporal lobe epilepsy600 - Technology::610 - Medicine & healthworking_paper10.48620/857463986817910.1101/2025.01.17.633277