Novel genes and sex differences in COVID-19 severity

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Instituto de Salud Carlos III (COV20_00622 to A.C., COV20/00792 to M.B., COV20_00181 to C.A., COV20_1144 to M.A.J.S., PI20/00876 to C.F.); European Union (ERDF) 'A way of making Europe'. Fundacion Amancio Ortega, Banco de Santander (to A.C.), Estrella de Levante S.A. and Colabora Mujer Association (to E.G.-N.) and Obra Social La Caixa (to R.B.); Agencia Estatal de Investigacion (RTC-2017-6471-1 to C.F.), Cabildo Insular de Tenerife (CGIEU0000219140 'Apuestas cientificas del ITER para colaborar en la lucha contra la COVID-19' to C.F.) and Fundacion Canaria Instituto de Investigacion Sanitaria de Canarias(PIFIISC20/57 to C.F.).

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Herrero-Gonzalez, AAuthorLopez-Rodriguez, RAuthorAyuso, CAuthor

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Novel genes and sex differences in COVID-19 severity

Publicated to:HUMAN MOLECULAR GENETICS. 31 (22): 3789-3806 - 2022-07-12 31(22), DOI: 10.1093/hmg/ddac132

Authors: Cruz R; Diz-De Almeida S; de Heredia ML; Quintela I; Ceballos FC; Pita G; Lorenzo-Salazar JM; González-Montelongo R; Gago-Domínguez M; Porras MS; Tenorio Castaño JA; Nevado J; Aguado JM; Aguilar C; Aguilera-Albesa S; Almadana V; Almoguera B; Alvarez N; Andreu-Bernabeu Á; Arana-Arri E; Arango C; Arranz MJ; Artiga MJ; Baptista-Rosas RC; Barreda-Sánchez M; Belhassen-Garcia M; Bezerra JF; Bezerra MAC; Boix-Palop L; Brion M; Brugada R; Bustos M; Calderón EJ; Carbonell C; Castano L; Castelao JE; Conde-Vicente R; Cordero-Lorenzana ML; Cortes-Sanchez JL; Corton M; Darnaude MT; De Martino-Rodríguez A; del Campo-Pérez V; de Bustamante AD; Domínguez-Garrido E; Luchessi AD; Eiros R; Estigarribia Sanabria GM; Fariñas MC; Fernández-Robelo U; Fernández-Rodríguez A; Fernández-Villa T; Gil-Fournier B; Gómez-Arrue J; Álvarez BG; de Quirós FGB; González-Peñas J; Gutiérrez-Bautista JF; Herrero MJ; Herrero-Gonzalez A; Jimenez-Sousa MA; Lattig MC; Borja AL; Lopez-Rodriguez R; Mancebo E; Martín-López C; Martín V; Martinez-Nieto O; Martinez-Lopez I; Martinez-Resendez MF; Martinez-Perez A; Mazzeu JF; Macías EM; Minguez P; Cuerda VM; Silbiger VN; Oliveira SF; Ortega-Paino E; Parellada M; Paz-Artal E; Santos NPC; Pérez-Matute P; Perez P; Pérez-Tomás ME; Perucho T; Pinsach-Abuin ML; Pompa-Mera EN; Porras-Hurtado GL; Pujol A; León SR; Resino S; Fernandes MR; Rodríguez-Ruiz E; Rodriguez-Artalejo F; Rodriguez-Garcia JA; Cabello FR; Ruiz-Hornillos J; Ryan P; Soria JM; Souto JC

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Azienda Osped Univ Senese, Genet Med, I-53100 Siena, Italy - Author

Bellvitge Biomed Res Inst IDIBELL, Neurometab Dis Lab, Lhospitalet De Llobregat 08908, Spain - Author

Biocruces Bizkai HRI, Baracaldo 48903, Bizkaia, Spain - Author

Biomed Res Inst St Pau IIB St Pau, Stroke Pharmacogenom & Genet Grp, Barcelona 08041, Spain - Author

Catalan Inst Res & Adv Studies ICREA, Barcelona 08010, Spain - Author

CIEN Fdn, Queen Sofia Fdn, Alzheimer Ctr, Madrid 28031, Spain - Author

Clin Comfamiliar Risaralda, Pereira 660003, Colombia - Author

Complejo Asistencial Univ Leon, Leon 24071, Spain - Author

Complejo Hosp Univ A Coruna CHUAC, Sistema Galego Saude SERGAS, Serv Med Intens, La Coruna 15009, Spain - Author

Complejo Hosp Univ A Coruna CHUAC, Urgencias Hosp, Sistema Galego Saude SERGAS, La Coruna 15009, Spain - Author

Cruces Univ Hosp, Osakidetza, Baracaldo 48903, Bizkaia, Spain - Author

Ctr Biomed Res La Rioja CIBIR, Infect Dis Microbiota & Metab Unit, Logrono 26006, Spain - Author

Ctr Med Nacl Siglo XXI, Inst Mexicano Seguro Social IMSS, Unidad Invest Med Enfermedades Infecciosas & Para, Mexico City 02990, DF, Mexico - Author

Ctr Para Desarrollo Invest Cient, Asuncion 1255, Paraguay - Author

ERN, ITHACA, European Reference Network, Amsterdam, Netherlands - Author

Escola Tecn Saude, Lab Vigilancia Mol Aplicada, BR-68515000 Brasilia, Para, Brazil - Author

Fdn Docencia I Recerca Mutua Terrassa, Terrassa 08221, Spain - Author

Fdn IRCCS CaGranda Osped Maggiore Policlin, Dept Transfus Med & Hematol, Precis Med, I-20122 Milan, Italy - Author

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Fdn Rioja Salud, Unidad Diagnost Mol, La Rioja 26006, Spain - Author

Fdn Santa Fe Bogota, Dept Pathol & Labs, Bogota 111711, Colombia - Author

Fdn Univ Ciencias Salud, Bogota 113827, Colombia - Author

Fonds Rech Sci FNRS, B-1000 Brussels, Belgium - Author

GENYCA, Madrid 28220, Spain - Author

Gregorio Maranon Hlth Res Inst IiSGM, Madrid 28007, Spain - Author

Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02114 USA - Author

Hosp Clin Univ Santiago CHUS, Sistema Galego Saude SERGAS, Unidad Cuidados Intens, Santiago De Compostela 15706, Spain - Author

Hosp Clin Univ Valladolid, Serv Anestesiol & Reanimac, Valladolid 47003, Spain - Author

Hosp Clin Univ Valladolid, Serv Hematol & Hemoterapia, Valladolid 47003, Spain - Author

Hosp Clin Univ Virgen Arrixaca, Serv Murciano Salud, Serv Pediat, Secc Genet Med, Murcia 30120, Spain - Author

Hosp El Bierzo, Unidad Cuidados Intens, Leon 24404, Spain - Author

Hosp Gen Occidente Seguro Social, Zapopan 45170, Jalisco, Mexico - Author

Hosp Gen Santa Barbara Soria, Soria 42005, Spain - Author

Hosp Gen Segovia, Med Intens, Segovia 40002, Spain - Author

Hosp Gen Univ Gregorio Maranon IiSGM, Inst Psychiat & Mental Hlth, Dept Child & Adolescent Psychiat, Madrid 28007, Spain - Author

Hosp Infanta Elena, Allergy Unit, Madrid 28342, Spain - Author

Hosp Josep Trueta, Cardiol Serv, Girona 17190, Spain - Author

Hosp Ninos Dr Ricardo Gutierrez, C1425EFD, Buenos Aires, DF, Argentina - Author

Hosp Ophir Loyola, Dept Ensino & Pesquisa, BR-66063240 Belem, Para, Brazil - Author

Hosp Santa Creu & Sant Pau, IIB St Pau, Haemostasis & Thrombosis Unit, Barcelona 08041, Spain - Author

Hosp Santa Creu & Sant Pau, Res Inst, IIB St Pau, Genom Complex Dis Unit, Barcelona 08041, Spain - Author

Hosp UM Valdecilla, Cantabria 39008, Spain - Author

Hosp Univ 12 Octubre, Dept Immunol, Madrid 28041, Spain - Author

Hosp Univ 12 Octubre, Inst Invest Sanitaria Hosp 12 Octubre imas12, Unit Infect Dis, Madrid 28041, Spain - Author

Hosp Univ Clin San Cecilio, Granada 18016, Spain - Author

Hosp Univ Getafe, Serv Genet, Madrid 28905, Spain - Author

Hosp Univ Infanta Leonor, Madrid 28031, Spain - Author

Hosp Univ La Paz IDIPAZ, Inst Genet Med & Mol INGEMM, Madrid 28046, Spain - Author

Hosp Univ Mostoles, Med Interna, Madrid 28935, Spain - Author

Hosp Univ Mostoles, Unidad Genet, Madrid 28935, Spain - Author

Hosp Univ Mutua Terrassa, Terrassa 08221, Spain - Author

Hosp Univ NS Candelaria, Res Unit, Santa Cruz De Tenerife 38010, Spain - Author

Hosp Univ Rio Hortega, Valladolid 47012, Spain - Author

Hosp Univ Salamanca IBSAL, Serv Cardiol, Salamanca 37007, Spain - Author

Hosp Univ Salamanca IBSAL, Serv Med Interna, Salamanca 37007, Spain - Author

Hosp Univ Salamanca IBSAL, Serv Med Interna, Unidad Enfermedades Infecciosas, Salamanca 37007, Spain - Author

Hosp Univ Son Espases, Unidad Diagnost Mol & Genet Clin, Islas Baleares 07120, Spain - Author

Hosp Univ Vall dHebron, Vall dHebron Barcelona Hosp Campus, Dept Internal Med, Liver Unit, Barcelona 08035, Spain - Author

Hosp Univ Valme, Unidad Clin Enfermedades Infecciosas & Microbiol, Seville 41014, Spain - Author

Hosp Univ Virgen Macarena, Neumol, Seville 41009, Spain - Author

Hosp Univ Virgen Nieves, Serv Anal Clin & Inmunol, Granada 18014, Spain - Author

Humanitas Univ, Dept Biomed Sci, I-20089 Milan, Italy - Author

IdiPaz Inst Invest Sanitaria Hosp Univ La Paz, Madrid 28046, Spain - Author

IDIVAL, Cantabria 39008, Spain - Author

IIS La Fe, Plataforma Farmacogenet, Valencia 46026, Spain - Author

Inditex, La Coruna 15141, Spain - Author

Inst Aragones Ciencias Salud IACS, Zaragoza 50009, Spain - Author

Inst Biomed Sevilla, Seville 41013, Spain - Author

Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona 08036, Spain - Author

Inst Invest Biomed Girona IDIBGI, Cardiovasc Genet Ctr, Girona 17190, Spain - Author

Inst Invest Biosanitaria Granada ibs Granada, Granada 18012, Spain - Author

Inst Invest Ibs, Granada 18012, Spain - Author

Inst Invest Sanitaria Aragon IIS Aragon, Zaragoza 50009, Spain - Author

Inst Invest Sanitaria Galicia Sur, Xerencia Xest Integrada Vigo Serv Galego Saude, Oncol & Genet Unit, Vigo 36312, Spain - Author

Inst Invest Sanitaria Galicia Sur, Xerencia Xest Integrada Vigo Serv Galego Saude, Prevent Med Dept, Vigo 36312, Spain - Author

Inst Invest Sanitaria Hosp 12 Octubre imas12, Transplant Immunol & Immunodeficiencies Grp, Madrid 28041, Spain - Author

Inst Invest Sanitaria Santiago IDIS, Santiago De Compostela 15706, Spain - Author

Inst Invest Sanitaria Santiago IDIS, Xenet Cardiovasc, Santiago De Compostela 15706, Spain - Author

Inst Murciano Invest Biosanitaria IMIB Arrixaca, Murcia, Spain - Author

Inst Salud Carlos III ISCIII, Ctr Nacl Microbiol CNM, Unidad Infecc Viral & Inmun, Madrid 28220, Spain - Author

Inst Salud Carlos III, Ctr Biomed Network Res Cardiovasc Dis CIBERCV, Madrid 28029, Spain - Author

Inst Salud Carlos III, Ctr Biomed Network Res Diabet & Metab Associated, Madrid 28029, Spain - Author

Inst Salud Carlos III, Ctr Biomed Network Res Epidemiol & Publ Hlth CIBE, Madrid 28029, Spain - Author

Inst Salud Carlos III, Ctr Biomed Network Res Hepat & Digest Dis CIBEREH, Madrid 28029, Spain - Author

Inst Salud Carlos III, Ctr Biomed Network Res Mental Hlth CIBERSAM, Madrid 28029, Spain - Author

Inst Salud Carlos III, Ctr Biomed Network Res Neurodegenerat Dis CIBERNE, Madrid 28029, Spain - Author

Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Grp Clin Vinculado, Madrid 28029, Spain - Author

Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Madrid 28029, Spain - Author

Inst Salud Carlos III, Ctr Biomed Network Res Resp Dis CIBERES, Madrid 28029, Spain - Author

Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Infecciosas CI, Madrid 28029, Spain - Author

Inst Salud Carlos III, Spanish Network Res Infect Dis REIPI RD16 0016 00, Madrid 28029, Spain - Author

Inst Tecnol & Energias Renovables, Genom Div, Santa Cruz De Tenerife 38600, Spain - Author

IRCCS Humanitas Res Hosp, I-20089 Milan, Italy - Author

Japan Soc Promot Sci, Tokyo 1020083, Japan - Author

Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden - Author

Karolinska Inst, Inst Environm Med, S-17165 Solna, Sweden - Author

Kings Coll London, Dept Twin Res, London WC2R 2LS, England - Author

Kyoto Univ, Grad Sch Med, Kyoto McGill Int Collaborat Sch Genom Med, Kyoto 6068501, Japan - Author

Liege Univ Hosp, CHU Liege, B-4000 Liege, Belgium - Author

LMU Munich Univ, Univ Hosp, Dept Psychiat, D-80539 Munich, Germany - Author

LMU Munich Univ, Univ Hosp, Inst Psychiat Phenom & Genom, D-80539 Munich, Germany - Author

Max Planck Inst Evolutionary Anthropol, D-04103 Leipzig, Germany - Author

McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 0G4, Canada - Author

McGill Univ, Dept Human Genet Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 0G4, Canada - Author

McGill Univ, Dept Human Genet, Montreal, PQ H3A 0G4, Canada - Author

McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada - Author

Minist Salud Ciudad Buenos Aires, C1425EFD, Buenos Aires, DF, Argentina - Author

Natl Spanish Res Council CSIC, Inst Biomed Res Barcelona IIBB, Barcelona 08028, Spain - Author

Navarra Hlth Serv Hosp, Dept Pediat, Pediat Neurol Unit, Pamplona 31008, Spain - Author

NavarraBioMed Res Grp, Navarra Hlth Serv, Pamplona 31008, Spain - Author

Osakidetza Basque Hlth Serv, Donostialdea Integrated Hlth Org, Clin Biochem Dept, San Sebastian 20006, Spain - Author

Oslo Univ Hosp, Dept Microbiol, N-0424 Oslo, Norway - Author

Oslo Univ Hosp, Dept Transplantat Med, Sect Gastroenterol, N-0424 Oslo, Norway - Author

Oslo Univ Hosp, Norwegian PSC Res Ctr, N-0424 Oslo, Norway - Author

Oslo Univ Hosp, Res Inst Internal Med, N-0318 Oslo, Norway - Author

Oslo Univ Hosp, Res Inst Internal Med, N-0424 Oslo, Norway - Author

Otto Von Guericke Univ, Dept Micrograv & Translat Regenerat Med, D-39106 Magdeburg, Germany - Author

SIGEN Alianza Univ Los Andes, Fdn Santa Fe Bogota, Bogota 111711, Colombia - Author

Spanish Natl Canc Res Ctr, CNIO Biobank, Madrid 28029, Spain - Author

Spanish Natl Canc Res Ctr, Familial Canc Clin Unit, Madrid 28029, Spain - Author

Spanish Natl Canc Res Ctr, Human Genotyping CEGEN Unit, Madrid 28029, Spain - Author

Tech Univ Munich, Helmholtz Zentrum Munchen, Inst Virol, D-85764 Munich, Germany - Author

Tech Univ Munich, Univ Hosp Rechts Isar, Sch Med, Dept Internal Med 2, D-80333 Munich, Germany - Author

Tecnol Monterrey, Escuela Med & Ciencias Salud, Monterrey 64718, Mexico - Author

Tecnol Monterrey, Monterrey 64718, Mexico - Author

UAM, CSIC, CEI, IMDEA Food Inst, Madrid 28049, Spain - Author

Unidad Genet & Genom Islas Baleares, Islas Baleares 07120, Spain - Author

Univ Autonoma Barcelona, Dept Med, Barcelona 08193, Spain - Author

Univ Autonoma Madrid, Fdn Jimenez Diaz Univ Hosp, Inst Invest Sanitaria, UAM,FJD,IIS, Madrid 28040, Spain - Author

Univ Autonoma Madrid, Fdn Jimenez Diaz Univ Hosp, Inst Invest Sanitaria, UAM,FJD,IIS,Data Anal Dept, Madrid 28040, Spain - Author

Univ Autonoma Madrid, Fdn Jimenez Diaz Univ Hosp, Inst Invest Sanitaria, UAM,FJD,IIS,Dept Genet & Genom, Madrid 28040, Spain - Author

Univ Autonoma Madrid, Sch Med, Dept Prevent Med & Publ Hlth, Madrid 28049, Spain - Author

Univ Basque Country, UPV EHU, Bizkaia 48903, Spain - Author

Univ Basque Country, UPV EHU, Donostia Univ Hosp, Biodonostia Hlth Res Inst,Dept Liver & Gastrointe, San Sebastian 20014, Spain - Author

Univ Basque Country, UPV EHU, Donostia Univ Hosp, Ikerbasque,Biodonostia Hlth Res Inst,Dept Liver &, San Sebastian 20014, Spain - Author

Univ Bonn, Univ Hosp Bonn, Med Fac, Inst Human Genet, D-53127 Bonn, Germany - Author

Univ Brasilia, Fac Med, BR-70910900 Brasilia, DF, Brazil - Author

Univ Brasilia, Programa Pos Grad Biol Anim, BR-70910900 Brasilia, DF, Brazil - Author

Univ Brasilia, Programa Pos Grad Ciencias Med, BR-70910900 Brasilia, DF, Brazil - Author

Univ Brasilia, Programa Pos Grad Ciencias Saude, BR-70910900 Brasilia, DF, Brazil - Author

Univ Brasilia, Programa Pos Grad Profiss Ensino Biol UnB, BR-70910900 Brasilia, DF, Brazil - Author

Univ Brasilia, Programa Pos Grad Profiss Ensino Biol, BR-70910900 Brasilia, DF, Brazil - Author

Univ Cantabria, Cantabria 39008, Spain - Author

Univ Catolica San Antonio Murcia UCAM, Murcia 30120, Spain - Author

Univ Complutense Madrid, Dept Immunol Ophthalmol & ENT, Madrid 28040, Spain - Author

Univ Complutense Madrid, Madrid 28040, Spain - Author

Univ Complutense, Sch Med, Madrid 28040, Spain - Author

Univ Copenhagen, Novo Nordisk Fdn, Ctr Prot Res, Fac Hlth & Med Sci,Dis Syst Biol, DK-2200 Copenhagen, Denmark - Author

Univ Fed Para, Nucl Pesquisas Oncol, BR-66075110 Belem, Para, Brazil - Author

Univ Fed Pernambuco, Genet Postgrad Program, BR-50670907 Recife, PE, Brazil - Author

Univ Fed Rio Grande do Norte, Dept Anal Clin & Toxicol, BR-59012570 Natal, RN, Brazil - Author

Univ Fernando Pessoa, Fac Ciencias Salud, Las Palmas Gran Canaria 35450, Spain - Author

Univ Francisco Vitoria, Fac Med, Madrid 28223, Spain - Author

Univ Francisco Vitoria, Madrid 28223, Spain - Author

Univ Girona, Sch Med, Med Sci Dept, Girona 17190, Spain - Author

Univ Granada, Dept Bioquim Biol Mol & Inmunol 3, Granada 18071, Spain - Author

Univ Granada, Pfizer, Andalusian Reg Govt, GENYO,Ctr Genom & Oncol Res, Granada 18016, Spain - Author

Univ Guadalajara, Ctr Invest Multidisciplinario Salud, Tonala 45425, Jalisco, Mexico - Author

Univ Guadalajara, Ctr Univ Tonala, Tonala 45425, Jalisco, Mexico - Author

Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki 00014, Finland - Author

Univ Helsinki, Inst Mol Med Finland, Helsinki 00014, Finland - Author

Univ Hosp Burgos, Burgos 09006, Spain - Author

Univ Hosp Schleswig Holstein, Campus Kiel, D-24118 Kiel, Germany - Author

Univ Int Catalunya, ACE Alzheimer Ctr Barcelona, Memory Clin, Barcelona 08028, Spain - Author

Univ Int Catalunya, ACE Alzheimer Ctr Barcelona, Res Ctr, Barcelona 80828, Spain - Author

Univ Kiel, Inst Clin Mol Biol, D-24118 Kiel, Germany - Author

Univ Leon, Inst Biomed IBIOMED, Grp Invest Interacc Gen Ambiente & Salud GIIGAS, Leon 24071, Spain - Author

Univ Leon, Inst Biomed IBIOMED, Leon 24071, Spain - Author

Univ Libre Bruxelles, Hop Erasme, Ctr Genet Humaine, B-1070 Brussels, Belgium - Author

Univ Liege, GIGA Inst, B-4000 Liege, Belgium - Author

Univ Los Andes, Fac Ciencias, Bogota 111711, Colombia - Author

Univ Milan, Dept Pathopgysiol & Transplantat, I-20126 Milan, Italy - Author

Univ Milan, Fdn IRCCS CaGranda Osped Maggiore Policlin, Dept Transfus Med & Hematol, I-20126 Milan, Italy - Author

Univ Milano Bicocca, I-20126 Milan, Italy - Author

Univ Murcia UMU, Fac Med, Dept Cirugia Pediat Obstet & Ginecol, Murcia 30100, Spain - Author

Univ Nacl Caaguazu, Inst Reg Invest Salud, HH36 J3Q, Caaguazu, Paraguay - Author

Univ Oslo, Inst Clin Med, N-0424 Oslo, Norway - Author

Univ Salamanca, Salamanca 37007, Spain - Author

Univ Santiago de Compostela, Ctr Nacl Genotipado CEGEN, Santiago De Compostela 15706, Spain - Author

Univ Santiago de Compostela, Ctr Singular Invest Med Mol & Enfermedades Cronic, Santiago De Compostela 15782, Spain - Author

Univ Sao Paulo, Med Sch, Heart Inst InCor, BR-05508070 Sao Paulo, Brazil - Author

Univ Seville, Hosp Univ Virgen Rocio, Dept Med, Seville 41013, Spain - Author

Univ Seville, Virgen Rocio Univ Hosp, Consejo Super Invest Cient CSIC, Inst Biomed Seville IBiS, Seville 41013, Spain - Author

Univ Seville, Virgen Rocio Univ Hosp, Inst Biomed Seville, Digest Dis Unit, Seville 41103, Spain - Author

Univ Siena, Competence Ctr, Dept Med Biotechnol, I-53100 Siena, Italy - Author

Univ Siena, Med Biotech Hub, I-53100 Siena, Italy - Author

Univ Siena, Med Genet, I-53100 Siena, Italy - Author

Univ Simon Bolivar, Fac Ciencias Salud, Barranquilla 080002, Colombia - Author

Univ Valencia, Dept Farmacol, Valencia 4610, Spain - Author

Univ Valladolid, CSIC, Inst Biomed & Genet Mol IBGM, Unidad Excelencia,Mucosal Immunol Lab, Valladolid 47005, Spain - Author

Univ Valladolid, Dept Cirugia, Valladolid 47005, Spain - Author

Uppsala Univ, Dept Surg Sci Anaesthesiol & Intens Care Med, S-75105 Uppsala, Sweden - Author

Vall dHebron Inst Recerca VHIR, Liver Dis, Barcelona 08035, Spain - Author

Abstract

Here, we describe the results of a genome-wide study conducted in 11939 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<5x10(-8)) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P= 1.3x10(-22) and P= 8.1x10(-12), respectively), and for variants in 9q21.32 near TLE1 only among females (P= 4.4x10(-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= 2.7x10(-8)) and ARHGAP33 (P= 1.3x10(-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=4.1x10(-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.

Keywords

Androgen receptorAssociationAutozygosityExpressionGeneticsHomozygosityInterferonLungRangeRuns

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal HUMAN MOLECULAR GENETICS due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine (Miscellaneous). Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 8.58. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

Field Citation Ratio (FCR) from Dimensions: 17.14 (source consulted: Dimensions May 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-05-09, the following number of citations:

WoS: 41
OpenCitations: 43

Impact and social visibility

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Argentina; Belgium; Brazil; Canada; Colombia; Denmark; Finland; Germany; Italy; Japan; Mexico; Netherlands; Norway; Paraguay; Sweden; United Kingdom; United States of America.

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Novel genes and sex differences in COVID-19 severity

Affiliations

Abstract

Keywords

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

Impact and social visibility

Leadership analysis of institutional authors