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GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19

231Citations signalées, ce qui n’est pas une note de qualité
426Institutions déclarées
17Pays d’affiliation déclarés

Rattachement africain : gb, cn, au, ca, ie, hk, es, mx, nl, co, br, de, py, ar, us, fr, sa. Niveau de preuve : code pays fourni par la source.

Le résumé fourni par la source

Abstract Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown 1 to be highly efficient for discovery of genetic associations 2 . Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group 3 . Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling ( JAK1 ), monocyte–macrophage activation and endothelial permeability ( PDE4A ), immunometabolism ( SLC2A5 and AK5 ), and host factors required for viral entry and replication ( TMPRSS2 and RAB2A ).

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Le contrôle bibliographique ouvert

DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.

Titre Crossref
GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19
Date Crossref
17/05/2023
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 il ne compte pas comme une seconde source scientifique indépendante.

Les institutions déclarées

Roslin InstituteWestern General HospitalCentre for Inflammation ResearchInstitute of Genetics and CancerThe Queen's Medical Research InstituteUniversity of EdinburghNHS TaysideNinewells HospitalWestlake UniversityThe University of QueenslandCentre for Human GeneticsUniversity of OxfordUniversity of LeedsGenomics EnglandEdinburgh Royal InfirmaryImperial College LondonQueen's UniversityKingston Health Sciences CentreUniversity College DublinSt. Vincent's University HospitalUniversity of LiverpoolAlder Hey Children's HospitalHealth Protection Research Unit in Emerging and Zoonotic Infections at University of LiverpoolUniversity of CambridgeQueen Mary University of LondonWilliam Harvey Research InstituteChinese University of Hong KongPrince of Wales HospitalQueen's University BelfastUniversity of UlsterRoyal Victoria HospitalCentre for Mental HealthUniversity College LondonImperial College Healthcare NHS TrustRoyal Hospital for ChildrenGlasgow Centre for Population HealthInstituto de Salud Carlos IIIHospital Universitario Nuestra Señora de CandelariaUniversidad Fernando Pessoa CanariasInstituto Tecnológico y de Energías RenovablesCentre for Biomedical Network Research on Rare DiseasesUniversidad de CantabriaMarqués de Valdecilla University HospitalInstituto de Investigación Marqués de ValdecillaTecnológico de MonterreyHospital Universitario La PazHospital La Paz Institute for Health ResearchHammersmith HospitalNIHR Research Delivery NetworkCambridge University Hospitals NHS Foundation TrustEdinburgh Cancer ResearchRoslin Cells (United Kingdom)Cumberland InfirmarySt Mary's HospitalSt. Mary's HospitalManchester Royal InfirmaryRoyal Liverpool University HospitalSun Yat-sen UniversitySt John's HospitalLeiden University Medical CenterSt Thomas' HospitalJames Cook University HospitalRoyal Shrewsbury HospitalPrincess Royal HospitalBarts Health NHS TrustPrincess Alexandra Hospital NHS TrustHomerton University Hospital NHS Foundation TrustWishaw General HospitalUniversity Hospital CrosshouseRoyal Stoke University HospitalRotherham General HospitalUniversity Hospital of WalesNorth Middlesex University Hospital NHS TrustPoole HospitalKing's College HospitalCharing Cross HospitalSt Mary's HospitalRussells Hall HospitalRoyal Hallamshire HospitalNorthern General HospitalKing George HospitalQueen's HospitalJohn Radcliffe HospitalLiverpool Heart and Chest HospitalAddenbrooke's HospitalSt George's HospitalWorcestershire Royal HospitalAlexandra HospitalRoyal Berkshire NHS Foundation TrustKingston HospitalQueen Alexandra HospitalFrimley Park HospitalRoyal Gwent HospitalDarent Valley HospitalRoyal Blackburn Teaching HospitalStepping Hill HospitalRoyal Surrey County HospitalNorthumbria Healthcare NHS Foundation TrustWest Cumberland HospitalCountess of Chester HospitalSalford Royal HospitalPinderfields HospitalCroydon University HospitalMorriston HospitalQueen Elizabeth University HospitalAiredale General HospitalRoyal Alexandra HospitalBroomfield HospitalHeartlands HospitalRoyal Sussex County HospitalUniversity Hospitals Sussex NHS Foundation TrustQueen Elizabeth Hospital BirminghamGood Hope HospitalYork HospitalGreat Ormond Street HospitalRoyal Glamorgan HospitalPrincess of Wales HospitalPrince Charles HospitalBarnet HospitalThe Royal Free HospitalWythenshawe HospitalMacclesfield District General HospitalMedway Maritime HospitalWhiston HospitalRoyal Oldham HospitalNorth Devon District HospitalFairfield General HospitalChesterfield Royal Hospital NHS Foundation TrustAberdeen Royal InfirmaryRoyal Devon and Exeter HospitalGlasgow Royal InfirmaryBlackpool Victoria HospitalSouthampton General HospitalSt Peter's HospitalDerriford HospitalEast Surrey HospitalLeeds General InfirmarySt James's University HospitalBedford HospitalMusgrove Park HospitalSouthport and Formby District General HospitalYsbyty Gwynedd Hospital NHS TrustMaidstone HospitalTunbridge Wells HospitalQueen Elizabeth HospitalNorth Manchester General HospitalUniversity Hospital LewishamRoyal Victoria InfirmaryWilliam Harvey HospitalHull Royal InfirmaryRoyal Brompton HospitalRoyal Derby HospitalAintree University HospitalNorfolk and Norwich University HospitalMilton Keynes HospitalQueen Elizabeth HospitalRoyal Bolton HospitalTameside HospitalUniversity Hospital of North TeesSouthmead HospitalWrexham Maelor HospitalArrowe Park HospitalRoyal Hampshire County HospitalBradford Royal InfirmaryGlan Clwyd HospitalRoyal Bournemouth HospitalBristol Royal InfirmaryUniversity Hospital of North DurhamDarlington Memorial HospitalBasildon HospitalUniversity College HospitalBarnsley HospitalWhittington HospitalNational Hospital for Neurology and NeurosurgeryIpswich HospitalCounty HospitalSunderland Royal HospitalBurton Hospitals NHS Foundation TrustDorset County HospitalPapworth HospitalWest Middlesex University HospitalWithybush General HospitalRoyal Albert Edward InfirmaryRoyal Preston HospitalStoke Mandeville HospitalRoyal Lancaster InfirmaryBasingstoke and North Hampshire HospitalFurness General HospitalWorthing HospitalHarefield HospitalSt Richard's HospitalRoyal Cornwall HospitalWatford General HospitalCraigavon Area HospitalKings Mill HospitalDumfries and Galloway Royal InfirmaryGreat Western HospitalLincoln County HospitalGlangwili General HospitalSouthend University Hospital NHS Foundation TrustLister HospitalDiana Princess of Wales HospitalBronglais General HospitalPrince Philip HospitalWest Suffolk HospitalVictoria HospitalCalderdale Royal HospitalScunthorpe General HospitalEaling HospitalNorthwick Park HospitalHuddersfield Royal InfirmaryRoyal United HospitalGeorge Eliot Hospital NHS TrustYeovil District HospitalForth Valley Royal HospitalChelsea and Westminster Hospital NHS Foundation TrustQueen Elizabeth the Queen Mother HospitalConquest HospitalEastbourne District General HospitalQueen Elizabeth Hospital King's Lynn NHS Foundation TrustHairmyres HospitalWalsall Manor HospitalWarrington HospitalSalisbury District HospitalGloucestershire Royal HospitalLeicester Royal InfirmaryPeterborough City HospitalColchester HospitalHinchingbrooke HospitalMonklands HospitalRoyal Manchester Children's HospitalNew Cross HospitalWarwick HospitalCity HospitalSandwell General HospitalUniversity Hospitals Coventry and Warwickshire NHS TrustTorbay HospitalPilgrim HospitalNorthampton General Hospital NHS TrustThe Christie NHS Foundation TrustJames Paget University HospitalBirmingham Children's HospitalRaigmore HospitalScarborough General HospitalBorders General HospitalLeighton HospitalKent and Canterbury HospitalHarrogate and District NHS Foundation TrustRoyal Marsden HospitalWexham Park HospitalSheffield Children's HospitalRoyal Alexandra Children's HospitalGolden Jubilee National HospitalHospital Universitario de MóstolesHospital de Sant PauHospital Universitario 12 De OctubreComplejo Hospitalario de NavarraComplejo Asistencial Universitario de PalenciaHospital San PedroUniversitat Autònoma de BarcelonaInstitut GuttmannHospital Universitario Virgen MacarenaUniversidad de SalamancaHospital Universitario Fundación Jiménez DíazUniversidad Autónoma de MadridSpanish National Cancer Research CentreUniversidad Francisco de VitoriaInstituto de Investigación Biomédica de SalamancaUniversidad Complutense de MadridCentro de Investigación Biomédica en RedRed Espanola de Investigacion en Patologia InfecciosaNavarrabiomedBioCruces Health research InstituteHospital Universitario Infanta LeonorInstitut d'Investigació en Ciències de la Salut Germans Trias i PujolHospital Universitario Infantil San JoséUniversidade Federal do Rio Grande do NorteUniversidade de BrasíliaUniversidad Simón BolívarCentro de Investigación del CáncerCentro de Investigación Biomédica en Red de CáncerUniversity Hospital Mútua de TerrassaMútua TerrassaFundación Santa Fe de BogotáHospital General Universitario Gregorio MarañónSecretaría de Salud de JaliscoHospital de CrucesInstituto Murciano de Investigación BiosanitariaCentro de Investigación Biomédica en Red de Salud MentalUniversidad FUCSHospital Universitario de FuenlabradaMinistry of EducationCentro de Estudos e Pesquisas em Educação, Cultura e Ação ComunitáriaColégio Brasileiro de CirurgiõesUniversidade Federal de PernambucoHospital Universitario del TajoSecretaría de Salud de BogotáAlcaldía de BarranquillaInstituto de Investigación Sanitaria de SantiagoCentro de Investigación en Red en Enfermedades CardiovascularesConsejo Superior de Investigaciones CientíficasUniversidad de GuadalajaraInstituto de Biomedicina de SevillaHospital Universitario Virgen del RocíoUniversidad de SevillaHospital Universitario Insular de Gran CanariaUniversidad Católica de MurciaUniversidad de Los AndesUniversidade de FortalezaUniversidade de São PauloAndalusian School of Public HealthCentro Nacional de MicrobiologiaUniversitat de GironaBellvitge University HospitalInstitut d'Investigació Biomèdica de GironaHospital Universitari de Girona Doctor Josep TruetaCentro de Investigación Biomédica en Red de Epidemiología y Salud PúblicaHospital Universitario Río HortegaComplexo Hospitalario Universitario A CoruñaServicio Gallego de SaludUniversitat de ValènciaOtto-von-Guericke-Universität MagdeburgInstitut d'Investigació Biomédica de BellvitgeUniversity of the Basque CountryCentro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas AsociadasOsakidetzaUniversidade de Santiago de CompostelaHospital Universitario Severo OchoaSpanish Biomedical Research Centre in Physiopathology of Obesity and NutritionInstituto Aragonés de Ciencias de la SaludCenter for Research in Molecular Medicine and Chronic DiseasesHospital Universitario Quirónsalud MadridHospital Universitario Puerta de Hierro MajadahondaInstituto de Investigación Sanitaria AragónUniversidad Nacional De CaaguazúUniversidade Federal do ParáUniversidad Nacional de AsunciónDr. Euryclides Hospital de Jesus ZerbiniUniversidad de LeónHospital Infantil Universitario Niño JesúsHospital Sant Joan de Déu BarcelonaInstituto de Ensino e Pesquisa Santa CasaFundación Pública Galega de Medicina XenómicaHospital General de Niños Ricardo GutierrezInstituto Ramón y Cajal de Investigación SanitariaHospital Universitario Ramón y CajalHospital Universitario de GetafeMinisterio de SaludHospital Clínico Universitario de ValladolidUniversidad de ValladolidSecretaria Municipal de SaúdeHospital Universitario Virgen de las NievesComplejo Hospitalario Universitario de SantiagoInstituto de Investigación Sanitaria La FeHospital Universitario Virgen de la ArrixacaUniversidad de MurciaCenter for Biomedical Research of La RiojaSabin Medicina Diagnostica (Brazil)Centro Dermatológico Federico Lleras AcostaUniversitat Pompeu FabraHospital General De SegoviaHospital Del MarHospital del Mar Research InstituteHospital Universitario de CanariasJunta de Castilla y LeónResearch Institute Hospital 12 de OctubreMadrid Institute for Advanced StudiesIMDEA FoodUniversidad de GranadaInstituto de Investigación Biosanitaria de GranadaUniversity of TorontoHospital Universitario Son EspasesHospital El BierzoInstituto de Investigación Sanitaria del Hospital Clínico San CarlosUniversidade Cruzeiro do SulIcesi UniversityHealth Research Institute of the Balearic IslandsHospital Nuestra Señora de AlarcosHospital Universitario Príncipe de AsturiasFundación Valle del LiliMexican Social Security InstituteCentro Medico Nacional Siglo XXIUniversidad de AlcaláInstituto de Pesquisas da MarinhaInstitució Catalana de Recerca i Estudis AvançatsHospital Universitario de Gran Canaria Doctor NegrínBiomedical Research InstituteHospital Universitari Germans Trias i PujolUniversidad Rey Juan CarlosNewcastle upon Tyne Hospitals NHS Foundation TrustNewcastle UniversityHospital Universitário Lauro WanderleyHospital Universitario de BurgosUniversidad de BurgosComunidad de MadridPublic Health EnglandMRC University of Glasgow Centre for Virus ResearchUniversity of SheffieldLiverpool School of Tropical MedicineUniversity of BirminghamLung InstituteMedawar Building for Pathogen ResearchNottingham University Hospitals NHS TrustCentre National de la Recherche ScientifiqueInsermUniversité de LilleInstitut Pasteur de LilleMcGill University and Génome Québec Innovation CentreEuropean Genomic Institute for DiabetesKing's College LondonSt Mary's HospitalWalton CentreClatterbridge Cancer Centre NHS Foundation TrustGuy's and St Thomas' NHS Foundation TrustNHS Greater Glasgow and ClydeNational Health ServicePublic Health ScotlandManchester Academic Health Science CentreUniversity of ManchesterOxford Research Group23andMe (United States)Age UKEmory University HospitalIntensive Care National Audit & Research CentreInstituto ButantanKing Fahd Medical City

Une affiliation ne permet pas de déduire la nationalité d’un auteur.

Les sujets associés

interferon and immune responsesEndoplasmic Reticulum Stress and DiseaseDiabetes and associated disorders

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