Evidence map›Paper›PMID 35708486›Full record

SynthesisHuman molecular genetics2022

Novel genes and sex differences in COVID-19 severity.

Raquel Cruz, Silvia Diz-de Almeida, Miguel López de Heredia, Inés Quintela, Francisco C Ceballos, Guillermo Pita, José M Lorenzo-Salazar, Rafaela González-Montelongo, Manuela Gago-Domínguez, Marta Sevilla Porras and 158 more

Open access · hybridAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Human molecular genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 3 pooled it
6.4field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 3 syntheses or guidelines pooled it, 66 citations in OpenAlex.

  1. Sex-stratified genome-wide meta-analysis identifies novel loci for cognitive decline in older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

168 authors at 20 institutions in 19 countries.

Raquel CruzCentro Nacional de Genotipado (CEGEN), Universidade de Santiago de Compostela, 15706 Santiago de Compostela, Spain.ORCID 0000-0002-6964-8898
Silvia Diz-de AlmeidaCentro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Miguel López de HerediaCentre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Inés QuintelaCentro Nacional de Genotipado (CEGEN), Universidade de Santiago de Compostela, 15706 Santiago de Compostela, Spain.
Francisco C CeballosUnidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain.
Guillermo PitaSpanish National Cancer Research Centre, Human Genotyping-CEGEN Unit, 28029 Madrid, Spain.
José M Lorenzo-SalazarGenomics Division, Instituto Tecnológico y de Energías Renovables, 38600 Santa Cruz de Tenerife, Spain.
Rafaela González-MontelongoGenomics Division, Instituto Tecnológico y de Energías Renovables, 38600 Santa Cruz de Tenerife, Spain.
Manuela Gago-DomínguezFundación Pública Galega de Medicina Xenómica, Sistema Galego de Saúde (SERGAS), 15706 Santiago de Compostela, Spain.
Marta Sevilla PorrasCentre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Jair Antonio Tenorio CastañoCentre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Julian NevadoCentre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Jose María AguadoUnit of Infectious Diseases, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain.
Carlos AguilarHospital General Santa Bárbara de Soria, 42005 Soria, Spain.
Sergio Aguilera-AlbesaPediatric Neurology Unit, Department of Pediatrics, Navarra Health Service Hospital, 31008 Pamplona, Spain.
Virginia AlmadanaHospital Universitario Virgen Macarena, Neumología, 41009 Seville, Spain.
Berta AlmogueraDepartment of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital - Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain.
Nuria AlvarezSpanish National Cancer Research Centre, Human Genotyping-CEGEN Unit, 28029 Madrid, Spain.
Álvaro Andreu-BernabeuDepartment of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón (IiSGM), 28007 Madrid, Spain.
Eunate Arana-ArriBiocruces Bizkai HRI, 48903 Barakaldo, Bizkaia, Spain.
Celso ArangoDepartment of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón (IiSGM), 28007 Madrid, Spain.
María J ArranzFundació Docència I Recerca Mutua Terrassa, 08221 Terrassa, Spain.
Maria-Jesus ArtigaSpanish National Cancer Research Center, CNIO Biobank, 28029 Madrid, Spain.
Raúl C Baptista-RosasHospital General de Occidente, 45170 Zapopan, Jalisco, Mexico.
María Barreda-SánchezInstituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), 30120 Murcia, Spain.
Moncef Belhassen-GarciaHospital Universitario de Salamanca-IBSAL, Servicio de Medicina Interna-Unidad de Enfermedades Infecciosas, 37007 Salamanca, Spain.
Joao F BezerraEscola Tecnica de Saúde, Laboratorio de Vigilancia Molecular Aplicada, 68515-000 Pará, Brazil.
Marcos A C BezerraFederal University of Pernambuco, Genetics Postgraduate Program, Recife 50670-907, PE, Brazil.
Lucía Boix-PalopHospital Universitario Mutua Terrassa, 08221 Terrassa, Spain.
María BrionInstituto de Investigación Sanitaria de Santiago (IDIS), Xenética Cardiovascular, 15706 Santiago de Compostela, Spain.ORCID 0000-0001-7463-2148
Ramón BrugadaCardiovascular Genetics Center, Institut d'Investigació Biomèdica Girona (IDIBGI), 17190 Girona, Spain.
Matilde BustosInstitute of Biomedicine of Seville (IBiS), Consejo Superior de Investigaciones Científicas (CSIC)- University of Seville- Virgen del Rocio University Hospital, 41013 Seville, Spain.
Enrique J CalderónDepartemento de Medicina, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, 41013 Seville, Spain.ORCID 0000-0002-3166-5086
Cristina CarbonellHospital Universitario de Salamanca-IBSAL, Servicio de Medicina Interna, 37007 Salamanca, Spain.
Luis CastanoBiocruces Bizkai HRI, 48903 Barakaldo, Bizkaia, Spain.
Jose E CastelaoOncology and Genetics Unit, Instituto de Investigacion Sanitaria Galicia Sur, Xerencia de Xestion Integrada de Vigo-Servizo Galego de Saúde, 36312 Vigo, Spain.
Rosa Conde-VicenteHospital Universitario Río Hortega, 47012 Valladolid, Spain.
M Lourdes Cordero-LorenzanaServicio de Medicina intensiva, Complejo Hospitalario Universitario de A Coruña (CHUAC), Sistema Galego de Saúde (SERGAS), 15009 A Coruña, Spain.
Jose L Cortes-SanchezTecnológico de Monterrey, 64718 Monterrey, Mexico.
Marta CortonDepartment of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital - Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain.
M Teresa DarnaudeHospital Universitario Mostoles, Unidad de Genética, 28935 Madrid, Spain.
Alba De Martino-RodríguezInstituto Aragonés de Ciencias de la Salud (IACS), 50009 Zaragoza, Spain.
Victor Del Campo-PérezPreventive Medicine Department, Instituto de Investigacion Sanitaria Galicia Sur, Xerencia de Xestion Integrada de Vigo-Servizo Galego de Saúde, 36312 Vigo, Spain.
Aranzazu Diaz de BustamanteHospital Universitario Mostoles, Unidad de Genética, 28935 Madrid, Spain.
Elena Domínguez-GarridoUnidad Diagnóstico Molecular. Fundación Rioja Salud, 26006 La Rioja, Spain.
Andre D LuchessiUniversidade Federal do Rio Grande do Norte, Departamento de Analises Clinicas e Toxicologicas, 59012-570 Natal, Brazil.
Rocío EirosHospital Universitario de Salamanca-IBSAL, Servicio de Cardiología, 37007 Salamanca, Spain.
Gladys Mercedes Estigarribia SanabriaInstituto Regional de Investigación en Salud-Universidad Nacional de Caaguazú, HH36+J3Q Caaguazú, Paraguay.
María Carmen FariñasIDIVAL, 39008 Cantabria, Spain.
Uxía Fernández-RobeloUrgencias Hospitalarias, Complejo Hospitalario Universitario de A Coruña (CHUAC), Sistema Galego de Saúde (SERGAS), 15009 A Coruña, Spain.
Amanda Fernández-RodríguezUnidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain.
Tania Fernández-VillaGrupo de Investigación en Interacciones Gen-Ambiente y Salud (GIIGAS) - Instituto de Biomedicina (IBIOMED), Universidad de León, 24071 León, Spain.
Belén Gil-FournierHospital Universitario de Getafe, Servicio de Genética, 28905 Madrid, Spain.
Javier Gómez-ArrueInstituto Aragonés de Ciencias de la Salud (IACS), 50009 Zaragoza, Spain.
Beatriz González ÁlvarezInstituto Aragonés de Ciencias de la Salud (IACS), 50009 Zaragoza, Spain.
Fernan Gonzalez Bernaldo de QuirósMinisterio de Salud Ciudad de Buenos Aires, Buenos Aires C1425EFD CABA, Argentina.
Javier González-PeñasDepartment of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón (IiSGM), 28007 Madrid, Spain.
Juan F Gutiérrez-BautistaHospital Universitario Virgen de las Nieves, Servicio de Análisis Clínicos e Inmunología, 18014 Granada, Spain.ORCID 0000-0003-1374-0756
María José HerreroIIS La Fe, Plataforma de Farmacogenética, 46026 Valencia, Spain.
Antonio Herrero-GonzalezData Analysis Department, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital - Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain.
María A Jimenez-SousaUnidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain.
María Claudia LattigUniversidad de los Andes, Facultad de Ciencias, Bogotá 111711, Colombia.
Anabel Liger BorjaHospital General de Segovia, Medicina Intensiva, 40002 Segovia, Spain.
Rosario Lopez-RodriguezDepartment of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital - Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain.
Esther ManceboHospital Universitario 12 de Octubre, Department of Immunology, 28041 Madrid, Spain.
Caridad Martín-LópezHospital General de Segovia, Medicina Intensiva, 40002 Segovia, Spain.
Vicente MartínInstituto de Biomedicina (IBIOMED), Universidad de León, 24071 León, Spain.
Oscar Martinez-NietoFundación Santa Fe de Bogota, Departamento Patologia y Laboratorios, Bogotá 111711, Colombia.
Iciar Martinez-LopezUnidad de Genética y Genómica Islas Baleares, 07120 Islas Baleares, Spain.
Michel F Martinez-ResendezTecnológico de Monterrey, 64718 Monterrey, Mexico.
Angel Martinez-PerezGenomics of Complex Diseases Unit, Research Institute of Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, 08041 Barcelona, Spain.
Juliana F MazzeuFaculdade de Medicina, Universidade de Brasília, Brasilia 70910-900, Brazil.
Eleuterio Merayo MacíasHospital El Bierzo, Unidad Cuidados Intensivos, 24404 León, Spain.
Pablo MinguezDepartment of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital - Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain.
Victor Moreno CuerdaHospital Universitario Mostoles, Medicina Interna, 28935 Madrid, Spain.
Vivian N SilbigerUniversidade Federal do Rio Grande do Norte, Departamento de Analises Clinicas e Toxicologicas, 59012-570 Natal, Brazil.
Silviene F OliveiraFaculdade de Medicina, Universidade de Brasília, Brasilia 70910-900, Brazil.
Eva Ortega-PainoSpanish National Cancer Research Center, CNIO Biobank, 28029 Madrid, Spain.
Mara ParelladaDepartment of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón (IiSGM), 28007 Madrid, Spain.
Estela Paz-ArtalHospital Universitario 12 de Octubre, Department of Immunology, 28041 Madrid, Spain.
Ney P C SantosUniversidade Federal do Pará, Núcleo de Pesquisas em Oncologia, Belém, Pará 66075-110, Brazil.
Patricia Pérez-MatuteInfectious Diseases, Microbiota and Metabolism Unit, Center for Biomedical Research of La Rioja (CIBIR), 26006 Logroño, Spain.
Patricia PerezInditex, 15141 A Coruña, Spain.
M Elena Pérez-TomásInstituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), 30120 Murcia, Spain.
Teresa PeruchoGENYCA, 28220 Madrid, Spain.
Mel Lina Pinsach-AbuinCardiovascular Genetics Center, Institut d'Investigació Biomèdica Girona (IDIBGI), 17190 Girona, Spain.
Ericka N Pompa-MeraInstituto Mexicano del Seguro Social (IMSS), Centro Médico Nacional Siglo XXI, Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Mexico City 02990, Mexico.
Gloria L Porras-HurtadoClinica Comfamiliar Risaralda, 660003 Pereira, Colombia.
Aurora PujolBellvitge Biomedical Research Institute (IDIBELL), Neurometabolic Diseases Laboratory, 08908 L'Hospitalet de Llobregat, Spain.
Soraya Ramiro LeónHospital Universitario de Getafe, Servicio de Genética, 28905 Madrid, Spain.
Salvador ResinoUnidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain.
Marianne R FernandesUniversidade Federal do Pará, Núcleo de Pesquisas em Oncologia, Belém, Pará 66075-110, Brazil.
Emilio Rodríguez-RuizUnidad de Cuidados Intensivos, Hospital Clínico Universitario de Santiago (CHUS), Sistema Galego de Saúde (SERGAS), 15706 Santiago de Compostela, Spain.
Fernando Rodriguez-ArtalejoDepartment of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
José A Rodriguez-GarciaComplejo Asistencial Universitario de León, 24071 León, Spain.
Francisco Ruiz CabelloHospital Universitario Virgen de las Nieves, Servicio de Análisis Clínicos e Inmunología, 18014 Granada, Spain.
Javier Ruiz-HornillosHospital Infanta Elena, Allergy Unit, Valdemoro, 28342 Madrid, Spain.
Pablo RyanHospital Universitario Infanta Leonor, 28031 Madrid, Spain.
José Manuel SoriaGenomics of Complex Diseases Unit, Research Institute of Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, 08041 Barcelona, Spain.
Juan Carlos SoutoHaemostasis and Thrombosis Unit, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, 08041 Barcelona, Spain.
Eduardo TamayoHospital Clinico Universitario de Valladolid, Servicio de Anestesiologia y Reanimación, 47003 Valladolid, Spain.
Alvaro Tamayo-VelascoHospital Clinico Universitario de Valladolid, Servicio de Hematologia y Hemoterapia, 47003 Valladolid, Spain.
Juan Carlos Taracido-FernandezData Analysis Department, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital - Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain.
Alejandro TeperHospital de Niños Ricardo Gutierrez, Buenos Aires C1425EFD CABA, Argentina.
Lilian Torres-TobarFundación Universitaria de Ciencias de la Salud, 113827 Bogotá, Colombia.
Miguel UriosteSpanish National Cancer Research Centre, Familial Cancer Clinical Unit, 28029 Madrid, Spain.
Juan Valencia-RamosUniversity Hospital of Burgos, 09006 Burgos, Spain.
Zuleima YáñezUniversidad Simón Bolívar, Facultad de Ciencias de la Salud, 080002 Barranquilla, Colombia.
Ruth ZarateCentro para el Desarrollo de la Investigación Científica, 1255 Asunción, Paraguay.
Tomoko NakanishiInstitute for Molecular Medicine Finland (FIMM), 00014 Univerisity of Helsinki, Finland.ORCID 0000-0001-9510-5646
Sara PigazziniUniversity of Milano-Bicocca, 20126 Milano, Italy.
Frauke DegenhardtInstitute of Clinical Molecular Biology, Christian-Albrechts-University, 24118 Kiel, Germany.ORCID 0000-0001-7516-3179
Guillaume Butler-LaporteDepartment of Epidemiology, Biostatistics and Occupational Health, McGill University, H3A 0G4 Montréal, Québec, Canada.ORCID 0000-0001-5388-0396
Douglas Maya-MilesDigestive Diseases Unit, Virgen del Rocio University Hospital, Institute of Biomedicine of Seville, University of Seville, 41103 Seville, Spain.
Luis BujandaDepartment of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014 San Sebastian, Spain.
Youssef BouysranCentre de Génétique Humaine, Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium.
Adriana PalomLiver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain.
David EllinghausNovo Nordisk Foundation Center for Protein Research, Disease Systems Biology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
Manuel Martínez-BuenoGENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, 18016 Granada, Spain.
Selina RolkerInstitute of Human Genetics, University Hospital Bonn, Medical Faculty University of Bonn, 53127 Bonn, Germany.
Sara AmitranoGenetica Medica, Azienda Ospedaliero-Universitaria Senese, 53100 Siena, Italy.
Luisa RoadeCentre for Biomedical Network Research on Hepatic and Digestive Diseases (CIBEREHD), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Francesca FavaUniversity of Siena, Medical Genetics, 53100 Siena, Italy.
Christoph D SpinnerTechnical University of Munich, School of Medicine, University Hospital rechts der Isar, Department of Internal Medicine II, 80333 Munich, Germany.ORCID 0000-0002-3875-5367
Daniele PratiDepartment of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, 20126 Milano, Italy.
David BernardoMucosal Immunology Lab, Unidad de Excelencia del Instituto de Biomedicina y Genética Molecular (IBGM, Universidad de Valladolid-CSIC), 47005 Valladolid, Spain.
Federico GarciaHospital Universitario Clinico San Cecilio, 18016 Granada, Spain.
Gilles DarcisUniversity of Liege. GIGA-Insitute, B- 4000 Liege, Belgium.
Israel Fernández-CadenasBiomedical Research Institute Sant Pau (IIB Sant Pau), Stroke Pharmacogenomics and Genetics Group, 08041 Barcelona, Spain.
Jan Cato HolterOslo University Hospital, Department of Microbiology, 0424 Oslo, Norway.
Jesus M BanalesDepartment of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), Ikerbasque, 20014 San Sebastian, Spain.
Robert FrithiofDepartment of Surgical Sciences, Anaesthesiology and Intensive Care Medicine, Uppsala University, 751 05 Uppsala, Sweden.
Stefano DugaHumanitas University, Department of Biomedical Sciences, 20089 Milan, Italy.
Rosanna AsseltaHumanitas University, Department of Biomedical Sciences, 20089 Milan, Italy.
Alexandre C PereiraHeart Institute (InCor)/University of Sao Paulo Medical School, 05508-070 Sao Paulo, Brazil.
Manuel Romero-GómezDigestive Diseases Unit, Virgen del Rocio University Hospital, Institute of Biomedicine of Seville, University of Seville, 41103 Seville, Spain.
Beatriz Nafría-JiménezOsakidetza Basque Health Service, Donostialdea Integrated Health Organisation, Clinical Biochemistry Department, 20006 San Sebastian, Spain.
Johannes R HovNorwegian PSC Research Center and Section of Gastroenterology, Dept Transplantation Medicine, Oslo University Hospital, 0424 Oslo, Norway.
Isabelle MigeotteFonds de la Recherche Scientifique (FNRS), B - 1000 Brussels.
Alessandra RenieriUniversity of Siena, Medical Genetics, 53100 Siena, Italy.ORCID 0000-0003-3818-0871
Anna M PlanasInstitute for Biomedical Research of Barcelona (IIBB), National Spanish Research Council (CSIC), 08028 Barcelona, Spain.
Kerstin U LudwigInstitute of Human Genetics, University Hospital Bonn, Medical Faculty University of Bonn, 53127 Bonn, Germany.ORCID 0000-0002-8541-2519
Maria ButiCentre for Biomedical Network Research on Hepatic and Digestive Diseases (CIBEREHD), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Souad RahmouniUniversity of Liege. GIGA-Insitute, B- 4000 Liege, Belgium.
Marta E Alarcón-RiquelmeGENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, 18016 Granada, Spain.
Eva C SchulteInstitute of Virology, Technical University Munich/Helmholtz Zentrum München, D-85764 Munich, Germany.
Andre FrankeInstitute of Clinical Molecular Biology, Christian-Albrechts-University, 24118 Kiel, Germany.
Tom H KarlsenNorwegian PSC Research Center and Section of Gastroenterology, Dept Transplantation Medicine, Oslo University Hospital, 0424 Oslo, Norway.
Luca ValentiUniversità degli Studi di Milano, Department of Pathopgysiology and Transplantation, 20126 Milano, Italy.
Hugo ZebergKarolinska Institutet, Department of Neuroscience, 171 77 Stockholm, Sweden.
Brent RichardsDepartment of Human Genetics, Epidemiology, Biostatistics and Occupational Health, McGill University, H3A 0G4 Montréal, Québec, Canada.
Andrea GannaInstitute for Molecular Medicine Finland, Univerisity of Helsinki, 00014 Helsinki, Finland.
Mercè BoadaResearch Center and Memory clinic, ACE Alzheimer Center Barcelona, Universitat Internacional de Catalunya, 08028 Barcelona, Spain.
Itziar de RojasResearch Center and Memory clinic, ACE Alzheimer Center Barcelona, Universitat Internacional de Catalunya, 08028 Barcelona, Spain.
Agustín RuizResearch Center and Memory clinic, ACE Alzheimer Center Barcelona, Universitat Internacional de Catalunya, 08028 Barcelona, Spain.
Pascual Sánchez-JuanCIEN Foundation/Queen Sofia Foundation Alzheimer Center, 28031 Madrid, Spain.
Luis Miguel RealHospital Universitario de Valme, Unidad Clínica de Enfermedades Infecciosas y Microbiología, 41014 Sevilla, Spain.
SCOURGE Cohort Group
HOSTAGE Cohort Group
GRA@CE Cohort Group
Encarna Guillen-NavarroInstituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), 30120 Murcia, Spain.
Carmen AyusoDepartment of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital - Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain.
Anna González-NeiraSpanish National Cancer Research Centre, Human Genotyping-CEGEN Unit, 28029 Madrid, Spain.
José A RianchoIDIVAL, 39008 Cantabria, Spain.
Augusto Rojas-MartinezTecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, 64718 Monterrey, Mexico.ORCID 0000-0003-3765-6778
Carlos FloresGenomics Division, Instituto Tecnológico y de Energías Renovables, 38600 Santa Cruz de Tenerife, Spain.
Pablo LapunzinaCentre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Angel CarracedoCentro Nacional de Genotipado (CEGEN), Universidade de Santiago de Compostela, 15706 Santiago de Compostela, Spain.
Instituto de Salud Carlos III · ESUniversidad Complutense de Madrid · ESSpanish National Cancer Research Centre · ESUniversidade de Santiago de Compostela · ESHospital de Sant Pau · ESHospital Universitario La Paz · ESInstituto de Investigación Sanitaria Aragón · ESOslo University Hospital · NOUniversidad de Cantabria · ESUniversitat Autònoma de Barcelona · ESChristian-Albrechts-Universität zu Kiel · DEComplexo Hospitalario Universitario A Coruña · ESHospital General De Segovia · ESHospital Universitario de Getafe · ESHospital Universitario de Móstoles · ESHospital Universitario Fundación Jiménez Díaz · ESHumanitas University · ITInstituto Murciano de Investigación Biosanitaria · ESInstituto Tecnológico y de Energías Renovables · ESKarolinska Institutet · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10-22 and P = 8.1 × 10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10-8) and ARHGAP33 (P = 1.3 × 10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.

Indexed as

COVID-19Genome-Wide Association StudyFemaleGenetic LociGenetic Predisposition to DiseaseHumansMaleMiddle AgedPolymorphism, Single NucleotideSex Characteristics

Identifiers

PMID35708486
PMCPMC9652109
OpenAlexW4283011053

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.