GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture
225Citations signalées — pas une note de qualité
203Institutions déclarées
31Pays d’affiliation déclarés
Résumé fourni par la source
Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture
- Date Crossref
- 31/08/2023
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude et ne compte pas comme une seconde source scientifique indépendante.
Institutions déclarées
University Medical Center UtrechtRoyal College of Surgeons in IrelandBroad InstituteHarvard UniversityMassachusetts General HospitalVanderbilt University Medical CenterUniversity of CologneUniversity Hospital CologneTel Aviv UniversityIstituto Giannina GasliniIstituti di Ricovero e Cura a Carattere ScientificoUniversity of GenoaThe Royal Melbourne HospitalThe University of MelbourneAlfred HealthMonash UniversityAneurin Bevan University Health BoardUniversity of TorontoInstitute for Biomedical Research and InnovationNational Research CouncilSt George’s University Hospitals NHS Foundation TrustNational Hospital for Neurology and NeurosurgeryUniversity College LondonWalter and Eliza Hall Institute of Medical ResearchParks VictoriaSwansea UniversityEpilepsy SocietyMeyer Children's HospitalUniversity of FlorenceUniversity Health NetworkInsermUniversity of FreiburgDiakonie KorkUniversity of Hong KongUniversity of BonnIstanbul UniversityUniversität UlmAustin HealthStichting Epilepsie Instellingen NederlandAmerican University of Beirut Medical CenterIstituto delle Scienze Neurologiche di BolognaUniversity of BolognaSheba Medical CenterUniversity of LuxembourgEuropean Patent OrganisationLudwig-Maximilians-Universität MünchenHertie Institute for Clinical Brain ResearchUniversity of TübingenChildren's Hospital of PhiladelphiaPraevium Research (United States)Universitätsmedizin GöttingenNational Institutes of HealthNational Human Genome Research InstituteThomas Jefferson University HospitalCooper Medical School of Rowan UniversityCleveland ClinicCleveland Clinic Lerner College of MedicineBoğaziçi UniversityBelfast Health and Social Care TrustFondazione IRCCS Istituto Neurologico Carlo BestaBethlehem UniversityMayo ClinicUniversité Paris CitéHôpital LariboisièreChang Gung UniversityLinkou Chang Gung Memorial HospitalThe University of SydneyChildren's Hospital at WestmeadCincinnati Children's Hospital Medical CenterFederico II University HospitalUniversité de MontréalUniversity of UlsterRoyal Victoria HospitalUniversity of HelsinkiInstitute for Molecular Medicine FinlandBeaumont HospitalUniversité Libre de BruxellesErasmus HospitalUniversité de LilleNYU Langone HealthSt. James's HospitalUniversity of PennsylvaniaHelsinki University HospitalVanderbilt UniversityNational Taiwan UniversityNeuroDevelopment CenterMedical University of ViennaMagna Graecia UniversityChristian-Albrechts-Universität zu KielUniversity Hospital Schleswig-HolsteinUniversity of LübeckNew York UniversitySaint Barnabas Medical CenterOslo University HospitalUniversity of OsloBaylor College of MedicineNationwide Children's HospitalLife & Brain (Germany)University of California, San FranciscoUniversity of North Carolina at Chapel HillUniversity of ZurichHasso Plattner InstituteIcahn School of Medicine at Mount SinaiFukuoka UniversityUniversité de StrasbourgUniversity of Southern DenmarkSwiss Epilepsy CenterNational Epilepsy CenterInstitute of Mental HealthImperial College LondonUniversity of Eastern FinlandKuopio University HospitalThe University of TokyoThe University of OsakaKocaeli ÜniversitesiPwani UniversityKenya Medical Research InstituteUniversity of OxfordSHOWA Medical University HospitalAmerican University of BeirutUniversity of OtagoGoethe University FrankfurtPhilipps University of MarburgUniversity of CalgaryAlberta Children's HospitalParacelsus Medical UniversitySchön Klinik VogtareuthCyprus Institute of Neurology and GeneticsUniversity of BernUniversity Hospital of BernYale UniversityLeipzig UniversitySt. Bonifatius HospitalHofstra UniversityChinese University of Hong KongUniversity of MessinaFolkhälsans ForskningscentrumLyon 1 UniversitéHospices Civils de LyonNewcastle upon Tyne Hospitals NHS Foundation TrustNewcastle UniversityHong Kong Polytechnic UniversityJanssen (United States)Helsinki Children's HospitalUniversidade Estadual de Campinas (UNICAMP)Brazilian Institute of Neuroscience and NeurotechnologyTseung Kwan O HospitaldeCODE Genetics (Iceland)University of LiverpoolEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentTrinity College DublinJustus-Liebig-Universität GießenGiessen School of TheologyRIKEN Center for Integrative Medical SciencesNational University Hospital of IcelandIstanbul University-CerrahpaşaRutgers, The State University of New JerseyJohnson UniversityAstraZeneca (United Kingdom)Swansea Bay University Health BoardMorriston HospitalBoston Children's HospitalAzienda USL di BolognaUniversity of CincinnatiUniversity of Cincinnati Medical CenterDuke UniversityCentre de Recherche en Neurosciences de LyonCentre Hospitalier Universitaire VaudoisCharité - Universitätsmedizin BerlinHospital of the University of PennsylvaniaBeth Israel Deaconess Medical CenterRoyal Children's HospitalUniversity Medical Center FreiburgUniversity of California San DiegoUniversity of GlasgowRush University Medical CenterUniversity Hospital of WalesAarhus UniversityThomas Jefferson UniversityThe Ohio State UniversityCanisius-Wilhelmina ZiekenhuisRIKEN Center for Brain ScienceNagoya City UniversityWashington University in St. LouisUniversity of BirminghamFondazione Istituto Neurologico Nazionale Casimiro MondinoKaohsiung Chang Gung Memorial HospitalVilnius UniversityMarmara UniversityUniversité Toulouse III - Paul SabatierCentre de recherche cerveau et cognitionJohns Hopkins UniversityJohns Hopkins MedicineAdmiraal De Ruyter ZiekenhuisUniversity of the WitwatersrandAgincourt Health and Socio-Demographic Surveillance SystemRWTH Aachen UniversityUniversity of AntwerpAntwerp University HospitalVIB-UAntwerp Center for Molecular NeurologyUniversity Hospital ZurichVivantes KlinikumBezmiâlem Vakıf Üniversitesi
Une affiliation ne permet pas de déduire la nationalité d’un auteur.
Sujets associés
Genetics and Neurodevelopmental DisordersGenomics and Rare DiseasesGenetic Associations and Epidemiology