{"doi":"10.1101/2025.01.17.633277","title":"Associations between epilepsy-related polygenic risk and brain morphology in childhood","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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":560559,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1243212,"name":"Lang Liu","orcid":"0000-0002-0348-2258","position":1,"is_corresponding":false},{"id":109385,"name":"Sara Larivière","orcid":"0000-0001-5701-1307","position":2,"is_corresponding":false},{"id":563619,"name":"Valeria Kebets","orcid":"0000-0003-1707-7437","position":3,"is_corresponding":false},{"id":1414767,"name":"Serena Fett","orcid":null,"position":4,"is_corresponding":false},{"id":880029,"name":"Clara F. 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