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Accès ouvert déclaré 2022 article

New insights into the genetic etiology of Alzheimer’s disease and related dementias

2595Citations signalées — pas une note de qualité
362Institutions déclarées
26Pays d’affiliation déclarés

Résumé fourni par la source

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.

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Contrôle bibliographique ouvert

DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.

Titre Crossref
New insights into the genetic etiology of Alzheimer’s disease and related dementias
Date Crossref
01/04/2022
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.

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InsermUniversité de LilleInstitut Pasteur de LilleCentre Hospitalier Universitaire de LilleFacteurs de risque et déterminants moléculaires des maladies liées au vieillissementUniversity of AntwerpVIB-UAntwerp Center for Molecular NeurologyAmsterdam NeuroscienceAmsterdam University Medical CentersVrije Universiteit AmsterdamUniversity of CologneUniversity Hospital BonnGerman Center for Neurodegenerative DiseasesInstituto de Salud Carlos IIIBiomedical Research Networking Center on Neurodegenerative DiseasesFundació ACEErasmus MCUniversity of OxfordErasmus University RotterdamUniversity of PennsylvaniaCardiff UniversityCommissariat à l'Énergie Atomique et aux Énergies AlternativesUniversité Paris-SaclayCentre National de Recherche en Génomique HumaineCEA Paris-SaclayUniversidade Federal do Rio Grande do NorteUniversity of Eastern FinlandBoston UniversityUniversity of WashingtonLeiden University Medical CenterUppsala UniversityStavanger University HospitalUniversidad de MálagaUniversitat Autònoma de BarcelonaHospital de Sant PauUniversity Hospital Mútua de TerrassaMútua TerrassaInstituto de Investigación Biosanitaria de GranadaHospital Universitario Central de AsturiasInstituto de Investigación Sanitaria del Principado de AsturiasUNSW SydneyCentre for Healthy Brain AgeingAristotle University of ThessalonikiGreek Association of Alzheimer's Disease and Related DisordersHospital Universitario Virgen de la ArrixacaAzienda Ospedaliera San GerardoUniversity of Milano-BicoccaFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoUniversity of BresciaHospital Universitari de Santa MariaInstituto de Investigación Biomédica de LleidaFundacion Centro De Investigacion De Enfermedades NeurologicasUniversity of MilanUniversity of OsloUniversité Paris CitéAssistance Publique – Hôpitaux de ParisHôpital BrocaMaladie d'Alzheimer : marqueurs génétiques et vasculaires, neuropsychologieFondazione Santa LuciaHospital Universitari i Politècnic La FeUniversity of ParmaMedical University of SofiaColumbia UniversityFramingham Heart StudyVanderbilt UniversityVanderbilt HealthThe University of Texas Health Science Center at HoustonCase Western Reserve UniversityCentro San Giovanni di Dio FatebenefratelliUniversité de MontpellierNeuropsychiatrie : Recherche Epidemiologique et CliniqueAzienda Ospedaliero-Universitaria CareggiUniversity of FlorenceAgostino Gemelli University PolyclinicIstituti di Ricovero e Cura a Carattere ScientificoBaylor College of MedicineUniversity of TurinNorwegian University of Science and TechnologySt Olav's University HospitalDementia Collaborative Research CentresNottingham Trent UniversityUniversidad de Buenos AiresInstitut für Schlaganfall- und DemenzforschungLudwig-Maximilians-Universität MünchenUniversity of AucklandUnidad Funcional de Investigación de Enfermedades CrónicasUniversité de BordeauxCentre Hospitalier Universitaire de BordeauxBordeaux Population HealthCentre d'Investigation Clinique Plurithématique de BordeauxUniversity of MiamiDr. John T. Macdonald FoundationUniversidade de Santiago de CompostelaFundación Pública Galega de Medicina XenómicaUniversity of PerugiaNormandie UniversitéGénomique du cancer et du cerveauUniversité de Rouen NormandieUniversity of CagliariRadboud University NijmegenRadboud University Medical CenterUniversity of ZurichHospital Universitario de ValmeUniversity of Bari Aldo MoroUniversity of ThessalyUniversity Medical Center GroningenIcahn School of Medicine at Mount SinaiMunich Cluster for Systems NeurologyTUM KlinikumTechnical University of MunichIcelandic Heart AssociationVrije Universiteit BrusselUniversitair Ziekenhuis BrusselIndiana University – Purdue University IndianapolisFondazione IRCCS Istituto Neurologico Carlo BestaGentofte HospitalUniversity of KentuckyTexas Tech UniversityUniversity College LondonTexas Tech University Health Sciences CenterUniversity of LisbonDonauspitalThe University of Texas at San Antonio Health Science CenterInstitute for Neurodegenerative DisordersUK Dementia Research InstituteNational Hospital for Neurology and NeurosurgeryInstituto de Biomedicina de SevillaHospital Universitario Virgen del RocíoUniversidad de SevillaHospital La Paz Institute for Health ResearchCentro de Biología Molecular Severo OchoaUniversidad Autónoma de MadridHospital Universitario La PazHeidelberg UniversityCentral Institute of Mental HealthInstituto Ramón y Cajal de Investigación SanitariaHospital Universitario Ramón y CajalMedical University of ViennaCentro Andaluz de Biología del DesarrolloKarolinska University HospitalKarolinska InstitutetStockholm UniversityUniversity of CambridgeETH ZurichUniversity Hospital ZurichSwiss Integrative Center for Human HealthUniversity of IcelandUniversity of NottinghamUniversity of CyprusSorbonne UniversitéPitié-Salpêtrière HospitalAlzheimer Precision MedicineUniversity of BonnUniversity of SouthamptonAllen Institute for Brain ScienceUniversity Medical Center UtrechtBrigham Young UniversityUniversity of BristolHässleholms SjukhusImperial College LondonUniversity of HelsinkiHelsinki University HospitalKuopio University HospitalFriedrich-Alexander-Universität Erlangen-NürnbergUniversitätsklinikum ErlangenUniversidad de CantabriaMarqués de Valdecilla University HospitalInstituto de Investigación Marqués de ValdecillaStockholm Gerontology Research Center FoundationNational Institutes of HealthInstitute on AgingNational Institute on AgingFinnish Institute for Health and WelfareCharles UniversityUniversity Hospital BrnoSt. Anne's University Hospital BrnoBiogipuzkoa Health Research InstituteBangor UniversityUniversità Cattolica del Sacro CuoreMRC Prion UnitUniversity of Duisburg-EssenHospital Clínic de BarcelonaBanc de Sang i TeixitsConsorci Institut D'Investigacions Biomediques August Pi I SunyerConsejo Nacional de Investigaciones Científicas y TécnicasUniversity of Mississippi Medical CenterInstitute for Medical ResearchDon Carlo Gnocchi FoundationUniversity of CopenhagenInstituto de Biomedicina de ValenciaInstituto de Investigación Sanitaria La FeCentre National de la Recherche ScientifiqueFreie Universität BerlinCharité - Universitätsmedizin BerlinHôpital Orthopédique de la Suisse RomandeUniversity of LausanneRigshospitaletMaastricht UniversityDelft University of TechnologyLeipzig UniversityUniversitätsklinikum WürzburgPrivatsykehuset HaugesundFonna Hospital TrustUniversity of BergenAzienda Ospedaliera Citta' della Salute e della Scienza di TorinoHospital Universitario de Gran Canaria Doctor NegrínUniversitat de BarcelonaNational and Kapodistrian University of AthensEginition HospitalUniversität HamburgUniversity Medical Center Hamburg-EppendorfZimmer Biomet (Germany)Oslo University HospitalOspedale Vito FazziHospital Clínico San CarlosCentro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas AsociadasNamsos HospitalKU LeuvenHarvard UniversityMcLean HospitalHarokopio University of AthensNa Homolce HospitalUniversity of OuluKing's College LondonQueen's Medical CentreQueen's University BelfastWellcome Sanger InstituteSt. James's HospitalDublin City UniversityQIMR Berghofer Medical Research InstituteManchester Academic Health Science CentreUniversity of ManchesterJohn Radcliffe HospitalHospital Clínico Universitario de ValenciaHertie Institute for Clinical Brain ResearchHospital El CruceHospital Privado de ComunidadUniversidad Nacional de La PampaInstituto de Neurología CognitivaHospital Universitario Son EspasesUniversity of the Basque CountryFundacion CITA AlzheimerNavarrabiomedHospital Universitario de La PrincesaStructure et Instabilité des GénomesInstitut de Psychiatrie et Neurosciences de ParisInstitut du CerveauNewcastle Hospitals - Campus for Ageing and VitalityNewcastle UniversityInstitut für Medizinische Biometrie, Informatik und EpidemiologieSomerset Partnership NHS Foundation TrustUniversity Hospital of WalesHelmholtz MunichSaarland UniversityUniversity of FreiburgUniversity Hospital HeidelbergAkershus University HospitalInnlandet Hospital TrustInstitute for Molecular Medicine FinlandAbbVie (United States)AstraZeneca (United Kingdom)Biogen (United States)GlaxoSmithKline (United Kingdom)Merck & Co., Inc., Rahway, NJ, USA (United States)Pfizer (United States)Sanofi (France)Maze (United States)Janssen (Belgium)University of TurkuTurku University HospitalVarsinais-Suomen SairaanhoitopiiriFinnish Red CrossHospital District of Helsinki and UusimaaBorealis (Finland)Northern Ostrobothnia Hospital DistrictTampere UniversityPirkanmaa Hospital DistrictTampere UniversityFinland UniversityCentral Finland Health Care DistrictUniversity of JyväskyläBusiness FinlandBristol-Myers Squibb (United States)Broad InstituteStanford UniversityThe University of Texas Southwestern Medical CenterThe University of Texas at AustinJohns Hopkins UniversityUniversity of MichiganMichigan MedicineMayo Clinic in FloridaUniversity of North TexasUniversity of North Texas Health Science CenterIndiana University School of MedicineUniversity of Wisconsin–MadisonGeriatric Research Education and Clinical CenterRush University Medical CenterBanner Sun Health Research InstituteUniversity of PittsburghHope Center for Neurological DisordersNorthwestern UniversityVA Puget Sound Health Care SystemMayo Clinic in ArizonaSwedish Medical CenterUniversity of California, San FranciscoUniversity of California San DiegoDuke UniversityUniversity of Kansas Medical CenterWashington University in St. LouisUniversity of South FloridaUSF Health Byrd Alzheimer's InstituteFred Hutch Cancer CenterBruce W. Carter VA Medical CenterUniversity of North Carolina at Chapel HillUniversity of California, Los AngelesUniversity of Southern CaliforniaWake Forest UniversityUniversity of California, IrvineColumbia University Irving Medical CenterUniversity of California, DavisMount Sinai Medical CenterUniversity of Alabama at BirminghamNew York UniversityMassachusetts General HospitalEmory HealthcareEmory UniversityWinnMedChildren's Hospital of PhiladelphiaBrigham and Women's HospitalVanderbilt University Medical CenterTranslational Genomics Research InstituteAlbert Einstein College of MedicineOregon Health & Science UniversityPortland VA Medical CenterKaiser Permanente Washington Health Research InstituteCleveland ClinicLou Ruvo Brain InstituteNational Center for PTSDUniversity of Colorado DenverUniversity of TorontoOccupational Cancer Research CentreYale UniversityRenaissance Computing InstituteCurtin UniversityUniversity of EdinburghSUNY Upstate Medical UniversityUniversitätsmedizin GreifswaldMedical University of GrazUniversity of Maryland, College ParkMonash UniversityUniversity of Colorado AnschutzInstitut des Maladies NeurodégénérativesJackson Memorial HospitalJohns Hopkins MedicineCentre Hospitalier Universitaire Sainte-JustineUniversité de MontréalHospital for Sick ChildrenSickKids FoundationThe Lundquist InstituteHarbor–UCLA Medical CenterBoston Medical CenterCologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases

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