Novel genes and sex differences in COVID-19 severity.


Por: Cruz R, Almeida SD, Heredia ML, Quintela I, Ceballos FC, Pita G, Lorenzo-Salazar JM, González-Montelongo R, Gago-Domínguez M, Porras MS, Castaño JAT, 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, Campo-Pérez V, Bustamante AD, Domínguez-Garrido E, Luchessi AD, Eiros R, Sanabria GME, Fariñas MC, Fernández-Robelo U, Fernández-Rodríguez A, Fernández-Villa T, Gil-Fournier B, Gómez-Arrue J, Álvarez BG, 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, Ruiz Cabello F, Ruiz-Hornillos J, Ryan P, Soria JM, Souto JC, Tamayo E, Tamayo-Velasco A, Taracido-Fernandez JC, Teper A, Torres-Tobar L, Urioste M, Valencia-Ramos J, Yáñez Z, Zarate R, Nakanishi T, Pigazzini S, Degenhardt F, Butler-Laporte G, Maya-Miles D, Bujanda L, Bouysran Y, Palom A, Ellinghaus D, Martínez-Bueno M, Rolker S, Amitrano S, Roade L, Fava F, Spinner CD, Prati D, Bernardo D, Garcia F, Darcis G, Fernández-Cadenas I, Holter JC, Banales JM, Frithiof R, Duga S, Asselta R, Pereira AC, Romero-Gómez M, Nafría-Jiménez B, Hov JR, Migeotte I, Renieri A, Planas AM, Ludwig KU, Buti M, Rahmouni S, Alarcón-Riquelme ME, Schulte EC, Franke A, Karlsen TH, Valenti L, Zeberg H, Richards B, Ganna A, Boada M, Rojas I, Ruiz A, Sánchez-Juan P, Real LM, Guillen-Navarro E, Ayuso C, González-Neira A, Riancho JA, Rojas-Martinez A, Flores C, Lapunzina P, Carracedo A

Publicada: 1 jun 2022 Ahead of Print: 16 jun 2022
Resumen:
Here we describe the results of a genome-wide study conducted in 11 939 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 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.

Direcciones
Cruz R: Centro Nacional de Genotipado (CEGEN), Universidade de Santiago de Compostela, Santiago de Compostela, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain; Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain
Almeida SD: Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain
Heredia ML: Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Quintela I: Centro Nacional de Genotipado (CEGEN), Universidade de Santiago de Compostela, Santiago de Compostela, Spain
Ceballos FC: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
Pita G: Human Genotyping-CEGEN Unit, Spanish National Cancer Research Centre, Madrid, Spain
Lorenzo-Salazar JM: Genomics Division, Instituto Tecnológico y de Energías Renovables, Santa Cruz de Tenerife, Spain
González-Montelongo R: Genomics Division, Instituto Tecnológico y de Energías Renovables, Santa Cruz de Tenerife, Spain
Gago-Domínguez M: Fundación Pública Galega de Medicina Xenómica, Sistema Galego de Saúde (SERGAS), Santiago de Compostela, Spain; Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain
Porras MS: Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz-IDIPAZ, Madrid, Spain
Castaño JAT: Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz-IDIPAZ, Madrid, Spain; ERN-ITHACA-European Reference Network
Nevado J: Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz-IDIPAZ, Madrid, Spain; ERN-ITHACA-European Reference Network
Aguado JM: Unit of Infectious Diseases, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain; Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0002), Instituto de Salud Carlos III, Madrid, Spain; School of Medicine, Universidad Complutense, Madrid, Spain; Centre for Biomedical Network Research on Infectious Diseases, Instituto de Salud Carlos III, Madrid, Spain
Aguilar C: Hospital General Santa Bárbara de Soria, Soria, Spain
Aguilera-Albesa S: Pediatric Neurology Unit, Department of Pediatrics, Navarra Health Service Hospital, Pamplona, Spain; Navarra Health Service, Navarra BioMed Research Group, Pamplona, Spain
Almadana V: Neumología, Hospital Universitario Virgen Macarena, Seville, Spain
Almoguera B: Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; Department of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital - Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
Alvarez N: Human Genotyping-CEGEN Unit, Spanish National Cancer Research Centre, Madrid, Spain
Andreu-Bernabeu Á: Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0002), Instituto de Salud Carlos III, Madrid, Spain; Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón (IiSGM), Madrid, Spain
Arana-Arri E: Biocruces Bizkai HRI, Bizkaia, Spain; Cruces University Hospital, Osakidetza, Bizkaia, Spain
Arango C: School of Medicine, Universidad Complutense, Madrid, Spain; Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón (IiSGM), Madrid, Spain; Centre for Biomedical Network Research on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
Arranz MJ: Fundació Docència I Recerca Mutua Terrassa, Barcelona, Spain
Artiga MJ: Spanish National Cancer Research Center, CNIO Biobank, Madrid, Spain
Baptista-Rosas RC: Hospital General de Occidente, Zapopan Jalisco, Mexico; Centro Universitario de Tonalá, Universidad de Guadalajara, Tonalá Jalisco, Mexico; Centro de Investigación Multidisciplinario en Salud, Universidad de Guadalajara, Tonalá Jalisco, Mexico
Barreda-Sánchez M: Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain; Universidad Católica San Antonio de Murcia (UCAM), Murcia, Spain
Belhassen-Garcia M: Servicio de Medicina Interna-Unidad de Enfermedades Infecciosas, Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain; Universidad de Salamanca, Salamanca, Spain
Bezerra JF: Escola Tecnica de Saúde, Laboratorio de Vigilancia Molecular Aplicada, Brazil
Bezerra MAC: Genetics Postgraduate Program, Federal University of Pernambuco, Recife, PE, Brazil
Boix-Palop L: Hospital Universitario Mutua Terrassa, Barcelona, Spain
Brion M: Xenética Cardiovascular, Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain; Centre for Biomedical Network Research on Cardiovascular Diseases (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
Brugada R: Centre for Biomedical Network Research on Cardiovascular Diseases (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain; Cardiovascular Genetics Center, Institut d'Investigació Biomèdica Girona (IDIBGI), Girona, Spain; Medical Science Department, School of Medicine, University of Girona, Girona, Spain; Cardiology Service, Hospital Josep Trueta, Girona, Spain
Bustos M: Institute of Biomedicine of Seville (IBiS), Consejo Superior de Investigaciones Científicas (CSIC)- University of Seville- Virgen del Rocio University Hospital, Seville, Spain
Calderón EJ: Departemento de Medicina, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Seville, Spain; Centre for Biomedical Network Research on Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Biomedicina de Sevilla, Seville, Spain
Carbonell C: Universidad de Salamanca, Salamanca, Spain; Servicio de Medicina Interna, Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain
Castano L: Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; Biocruces Bizkai HRI, Bizkaia, Spain; Osakidetza, Cruces University Hospital, Bizkaia, Spain; Centre for Biomedical Network Research on Diabetes and Metabolic Associated Diseases (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain; University of Pais Vasco, UPV/EHU, Bizkaia, Spain
Castelao JE: Oncology and Genetics Unit, Instituto de Investigacion Sanitaria Galicia Sur, Xerencia de Xestion Integrada de Vigo-Servizo Galego de Saúde, Vigo, Spain
Conde-Vicente R: Hospital Universitario Río Hortega, Valladolid, Spain
Cordero-Lorenzana ML: Servicio de Medicina intensiva, Complejo Hospitalario Universitario de A Coruña (CHUAC), Sistema Galego de Saúde (SERGAS), A Coruña, Spain
Cortes-Sanchez JL: Tecnológico de Monterrey, Monterrey, Mexico; Departament of Microgravity and Translational Regenerative Medicine, Otto von Guericke University, Magdeburg, Germany
Corton M: Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; Department of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital - Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
Darnaude MT: Unidad de Genética, Hospital Universitario Mostoles, Madrid, Spain
De Martino-Rodríguez A: Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain; Instituto Investigación Sanitaria Aragón (IIS-Aragon), Zaragoza, Spain
Campo-Pérez V: Preventive Medicine Department, Instituto de Investigacion Sanitaria Galicia Sur, Xerencia de Xestion Integrada de Vigo-Servizo Galego de Saúde, Vigo, Spain
Bustamante AD: Unidad de Genética, Hospital Universitario Mostoles, Madrid, Spain
Domínguez-Garrido E: Unidad Diagnóstico Molecular, Fundación Rioja Salud, La Rioja, Spain
Luchessi AD: Departamento de Analises Clinicas e Toxicologicas, Universidade Federal do Rio Grande do Norte, Natal, Brazil
Eiros R: Servicio de Cardiología, Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain
Sanabria GME: Instituto Regional de Investigación en Salud-Universidad Nacional de Caaguazú, Caaguazú, Paraguay
Fariñas MC: IDIVAL, Cantabria, Spain; Universidad de Cantabria, Cantabria, Spain; Hospital U M Valdecilla, Cantabria, Spain
Fernández-Robelo U: Urgencias Hospitalarias, Complejo Hospitalario Universitario de A Coruña (CHUAC), Sistema Galego de Saúde (SERGAS), A Coruña, Spain
Fernández-Rodríguez A: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
Fernández-Villa T: Grupo de Investigación en Interacciones Gen-Ambiente y Salud (GIIGAS) - Instituto de Biomedicina (IBIOMED), Universidad de León, León, Spain
Gil-Fournier B: Unidad de Genética, Hospital Universitario de Getafe, Madrid, Spain
Gómez-Arrue J: Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain; Instituto Investigación Sanitaria Aragón (IIS-Aragon), Zaragoza, Spain
Álvarez BG: Instituto Aragonés de Ciencias de la Salud (IACS), Zaragoza, Spain; Instituto Investigación Sanitaria Aragón (IIS-Aragon), Zaragoza, Spain
Quirós FGB: Ministerio de Salud Ciudad de Buenos Aires, Buenos Aires, Argentina
González-Peñas J: Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón (IiSGM), Madrid, Spain; School of Medicine, Universidad Complutense, Madrid, Spain; Centre for Biomedical Network Research on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
Gutiérrez-Bautista JF: Servicio de Análisis Clínicos e Inmunología, Hospital Universitario Virgen de las Nieves, Granada, Spain
Herrero MJ: Plataforma de Farmacogenética, IIS La Fe, Valencia, Spain; Departamento de Farmacología, Universidad de Valencia, Valencia, Spain
Herrero-Gonzalez A: Data Analysis Department, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital - Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
Jimenez-Sousa MA: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
Lattig MC: Facultad de Ciencias, Universidad de los Andes, Bogotá, Colombia; SIGEN Alianza Universidad de los Andes - Fundación Santa Fe de Bogotá, Bogotá, Colombia
Borja AL: Medicina Intensiva, Hospital General de Segovia, Segovia, Spain
Lopez-Rodriguez R: Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; Department of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital - Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
Mancebo E: Department of Immunology, Hospital Universitario 12 de Octubre, Madrid, Spain; Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Transplant Immunology and Immunodeficiencies Group, Madrid, Spain
Martín-López C: Medicina Intensiva, Hospital General de Segovia, Segovia, Spain
Martín V: Centre for Biomedical Network Research on Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Biomedicina (IBIOMED), Universidad de León, León, Spain
Martinez-Nieto O: SIGEN Alianza Universidad de los Andes - Fundación Santa Fe de Bogotá, Bogotá, Colombia; Departamento Patologia y Laboratorios, Fundación Santa Fe de Bogota, Bogotá, Colombia
Martinez-Lopez I: Unidad de Genética y Genómica Islas Baleares, Islas Baleares, Spain; Unidad de Diagnóstico Molecular y Genética Clínica, Hospital Universitario Son Espases, Islas Baleares, Spain
Martinez-Resendez MF: Tecnológico de Monterrey, Monterrey, Mexico
Martinez-Perez A: Genomics of Complex Diseases Unit, Research Institute of Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain
Mazzeu JF: Faculdade de Medicina, Universidade de Brasília, Brazil; Programa de Pós-Graduação em Ciências Médicas (UnB), Brazil; Programa de Pós-Graduação em Ciencias da Saude (UnB), Brazil
Macías EM: Unidad Cuidados Intensivos, Hospital El Bierzo, León, Spain
Minguez P: Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; Department of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital - Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
Cuerda VM: Medicina Interna, Hospital Universitario Mostoles, Madrid, Spain; Universidad Francisco de Vitoria, Madrid, Spain
Silbiger VN: Departamento de Analises Clinicas e Toxicologicas, Universidade Federal do Rio Grande do Norte, Natal, Brazil
Oliveira SF: Programa de Pós-Graduação em Ciencias da Saude (UnB), Brazil; Departamento de Genética e Morfologia, Instituto de Ciências Biológicas, Universidade de Brasília, Brazil; Programa de Pós-Graduação em Biologia Animal (UnB), Brazil; Programa de Pós-Graduação Profissional em Ensino de Biologia (UnB), Brazil
Ortega-Paino E: Spanish National Cancer Research Center, CNIO Biobank, Madrid, Spain
Parellada M: School of Medicine, Universidad Complutense, Madrid, Spain; Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón (IiSGM), Madrid, Spain; Centre for Biomedical Network Research on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
Paz-Artal E: Department of Immunology, Hospital Universitario 12 de Octubre, Madrid, Spain; Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Transplant Immunology and Immunodeficiencies Group, Madrid, Spain; Department of Immunology, Ophthalmology and ENT, Universidad Complutense de Madrid, Madrid, Spain
Santos NPC: Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, Brazil
Pérez-Matute P: Infectious Diseases, Microbiota and Metabolism Unit, Center for Biomedical Research of La Rioja (CIBIR), Logroño, Spain
Perez P: Inditex, A Coruña, Spain
Pérez-Tomás ME: Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain
Perucho T: GENYCA, Madrid, Spain
Pinsach-Abuin ML: Cardiovascular Genetics Center, Institut d'Investigació Biomèdica Girona (IDIBGI), Girona, Spain; Centre for Biomedical Network Research on Cardiovascular Diseases (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
Pompa-Mera EN: Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Instituto Mexicano del Seguro Social (IMSS), Centro Médico Nacional Siglo XXI, Mexico City, Mexico
Porras-Hurtado GL: Clinica Comfamiliar Risaralda, Pereira, Colombia
Pujol A: Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; Bellvitge Biomedical Research Institute (IDIBELL), Neurometabolic Diseases Laboratory, L'Hospitalet de Llobregat, Spain; Catalan Institution of Research and Advanced Studies (ICREA), Barcelona, Spain
León SR: Unidad de Genética, Hospital Universitario de Getafe, Madrid, Spain
Resino S: Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
Fernandes MR: Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, Brazil; Departamento de Ensino e Pesquisa, Hospital Ophir Loyola, Belém, Pará, Brazil
Rodríguez-Ruiz E: Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain; Unidad de Cuidados Intensivos, Hospital Clínico Universitario de Santiago (CHUS), Sistema Galego de Saúde (SERGAS), Santiago de Compostela, Spain
Rodriguez-Artalejo F: Centre for Biomedical Network Research on Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain; Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain; IdiPaz (Instituto de Investigación Sanitaria Hospital Universitario La Paz), Madrid, Spain; IMDEA-Food Institute, CEI UAM+CSIC, Madrid, Spain
Rodriguez-Garcia JA: Complejo Asistencial Universitario de León, León, Spain
Ruiz Cabello F: Servicio de Análisis Clínicos e Inmunología, Hospital Universitario Virgen de las Nieves, Granada, Spain; Instituto de Investigación Biosanitaria de Granada (ibs GRANADA), Granada, Spain; Departamento Bioquímica, Biología Molecular e Inmunología III, Universidad de Granada, Granada, Spain
Ruiz-Hornillos J: Allergy Unit, Valdemoro, Hospital Infanta Elena, Madrid, Spain; Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital - Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain; Faculty of Medicine, Universidad Francisco de Vitoria, Madrid, Spain
Ryan P: Hospital Universitario Infanta Leonor, Madrid, Spain; Complutense University of Madrid, Madrid, Spain; Gregorio Marañón Health Research Institute (IiSGM), Madrid, Spain
Soria JM: Genomics of Complex Diseases Unit, Research Institute of Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain
Souto JC: Haemostasis and Thrombosis Unit, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain
Tamayo E: Servicio de Anestesiologia y Reanimación, Hospital Clinico Universitario de Valladolid, Valladolid, Spain; Departamento de Cirugía, Universidad de Valladolid, Valladolid, Spain
Tamayo-Velasco A: Servicio de Hematologia y Hemoterapia, Hospital Clinico Universitario de Valladolid, Valladolid, Spain
Taracido-Fernandez JC: Data Analysis Department, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital - Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
Teper A: Hospital de Niños Ricardo Gutierrez, Buenos Aires, Argentina
Torres-Tobar L: Sociedad de Cirugía de Bogotá, Hospital de San José, Bogotá, Colombia
Urioste M: Familial Cancer Clinical Unit, Spanish National Cancer Research Centre, Madrid, Spain
Valencia-Ramos J: University Hospital of Burgos, Burgos, Spain
Yáñez Z: Facultad de Ciencias de la Salud, Universidad Simón Bolívar, Barranquilla, Colombia
Zarate R: Centro para el Desarrollo de la Investigación Científica, Paraguay
Nakanishi T: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland; Department of Human Genetics, McGill University, Montréal, Québec, Canada; Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Québec, Canada; Kyoto-McGill International Collaborative School in Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Research Fellow, Japan Society for the Promotion of Science, Japan
Pigazzini S: University of Milano-Bicocca, Milano, Italy; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
Degenhardt F: Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany; University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
Butler-Laporte G: Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Québec, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Québec, Canada
Maya-Miles D: Digestive Diseases Unit, Virgen del Rocio University Hospital, Institute of Biomedicine of Seville, University of Seville, Seville, Spain; Centre for Biomedical Network Research on Hepatic and Digestive Diseases (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
Bujanda L: Centre for Biomedical Network Research on Hepatic and Digestive Diseases (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain; Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain
Bouysran Y: Centre de Génétique Humaine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
Palom A: Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Departament de Medicina, Universitat Autònoma de Barcelona, Bellatera, Barcelona, Spain; Liver Diseases, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain
Ellinghaus D: Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany; Novo Nordisk Foundation Center for Protein Research, Disease Systems Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Martínez-Bueno M: GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain
Rolker S: Institute of Human Genetics, University Hospital Bonn, Medical Faculty University of Bonn, Bonn, Germany
Amitrano S: Genetica Medica, Azienda Ospedaliero-Universitaria Senese, Italy
Roade L: Centre for Biomedical Network Research on Hepatic and Digestive Diseases (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Universitat Autònoma de Barcelona, Departament de Medicina, Bellatera, Barcelona, Spain
Fava F: Medical Genetics, University of Siena, Italy; Azienda Ospedaliero-Universitaria Senese, Genetica Medica, Italy; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Italy
Spinner CD: Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Department of Internal Medicine II, Munich, Germany
Prati D: Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy
Bernardo D: Centre for Biomedical Network Research on Hepatic and Digestive Diseases (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain; Mucosal Immunology Lab, Unidad de Excelencia del Instituto de Biomedicina y Genética Molecular (IBGM, Universidad de Valladolid-CSIC), Valladolid, Spain
Garcia F: Hospital Universitario Clinico San Cecilio, Granada, Spain; Instituto de Investigación Ibs.Granada, Granada, Spain
Darcis G: University of Liege. GIGA-Insitute, Liege, Belgium; Liege University Hospital (CHU of Liege), Liege, Belgium
Fernández-Cadenas I: Biomedical Research Institute Sant Pau (IIB Sant Pau), Stroke Pharmacogenomics and Genetics Group, Barcelona, Spain
Holter JC: Department of Microbiology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Banales JM: Centre for Biomedical Network Research on Hepatic and Digestive Diseases (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain; Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), Ikerbasque, San Sebastian, Spain
Frithiof R: Department of Surgical Sciences, Anaesthesiology and Intensive Care Medicine, Uppsala University, Uppsala, Sweden
Duga S: Department of Biomedical Sciences, Humanitas University, Milan, Italy; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
Asselta R: Department of Biomedical Sciences, Humanitas University, Milan, Italy; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
Pereira AC: Heart Institute (InCor)/Univ Sao Paulo Med Sch, Sao Paulo, Brazil
Romero-Gómez M: Digestive Diseases Unit, Virgen del Rocio University Hospital, Institute of Biomedicine of Seville, University of Seville, Seville, Spain; Centre for Biomedical Network Research on Hepatic and Digestive Diseases (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
Nafría-Jiménez B: Osakidetza Basque Health Service, Donostialdea Integrated Health Organisation, Clinical Biochemistry Department, San Sebastian, Spain
Hov JR: Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Norwegian PSC Research Center and Section of Gastroenterology, Dept Transplantation Medicine, Oslo University Hospital, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
Migeotte I: Centre de Génétique Humaine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; Fonds de la Recherche Scientifique (FNRS)
Renieri A: Medical Genetics, University of Siena, Italy; Azienda Ospedaliero-Universitaria Senese, Genetica Medica, Italy; Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, University of Siena, Italy
Planas AM: Institute for Biomedical Researhc of Barcelona (IIBB), National Spanish Research Council (CSIC), Barcelona, Spain; Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Ludwig KU: Institute of Human Genetics, University Hospital Bonn, Medical Faculty University of Bonn, Bonn, Germany
Buti M: Centre for Biomedical Network Research on Hepatic and Digestive Diseases (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; Universitat Autònoma de Barcelona, Departament de Medicina, Bellatera, Barcelona, Spain
Rahmouni S: University of Liege. GIGA-Insitute, Liege, Belgium
Alarcón-Riquelme ME: GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain; Institute for Environmental Medicine, Karolinska Institutet, Solna, Sweden
Schulte EC: Institute of Virology, Technical University Munich/Helmholtz Zentrum München, Munich, Germany; Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich University, Munich, Germany; Department of Psychiatry, University Hospital, LMU Munich University, Munich, Germany
Franke A: Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany; University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
Karlsen TH: Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Norwegian PSC Research Center and Section of Gastroenterology, Dept Transplantation Medicine, Oslo University Hospital, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
Valenti L: Department of Pathopgysiology and Transplantation, Università degli Studi di Milano, Milano, Italy; Department of Transfusion Medicine and Hematology, Precision Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
Zeberg H: Department of Neuroscience, Karolinska Institutet, Sweden; Max-Planck Institute for Evolutionary Anthropology, Leipzig, Germany
Richards B: Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Québec, Canada; Department of Human Genetics, Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Québec, Canada; King's College London, Department of Twin Research, London, United Kingdom
Ganna A: Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland; Massachusetts General Hospital, Harvard Medical School, Boston, USA
Boada M: Research Center and Memory clinic, ACE Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Spain; Centre for Biomedical Network Research on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain
Rojas I: Research Center and Memory clinic, ACE Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Spain; Centre for Biomedical Network Research on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain
Ruiz A: Research Center and Memory clinic, ACE Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Spain; Centre for Biomedical Network Research on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain
Sánchez-Juan P: CIEN Foundation/Queen Sofia Foundation Alzheimer Center, Madrid, Spain
Real LM: Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Sevilla, Spain
Guillen-Navarro E: Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), Murcia, Spain; Sección Genética Médica - Servicio de Pediatría, Hospital Clínico Universitario Virgen de la Arrixaca, Servicio Murciano de Salud, Murcia, Spain; Departamento Cirugía, Pediatría, Obstetricia y Ginecología, Facultad de Medicina, Universidad de Murcia (UMU), Murcia, Spain; Grupo Clínico Vinculado, Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Ayuso C: Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; Department of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital - Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid, Spain
González-Neira A: Human Genotyping-CEGEN Unit, Spanish National Cancer Research Centre, Madrid, Spain
Riancho JA: IDIVAL, Cantabria, Spain; Universidad de Cantabria, Cantabria, Spain; Hospital U M Valdecilla, Cantabria, Spain
Rojas-Martinez A: Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Mexico
Flores C: Genomics Division, Instituto Tecnológico y de Energías Renovables, Santa Cruz de Tenerife, Spain; Research Unit, Hospital Universitario N.S. de Candelaria, Santa Cruz de Tenerife, Spain; Centre for Biomedical Network Research on Respiratory Diseases (CIBERES), Instituto de Salud Carlos III, Madrid, Spain
Lapunzina P: Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz-IDIPAZ, Madrid, Spain; ERN-ITHACA-European Reference Network
Carracedo A: Centro Nacional de Genotipado (CEGEN), Universidade de Santiago de Compostela, Santiago de Compostela, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; Fundación Pública Galega de Medicina Xenómica, Sistema Galego de Saúde (SERGAS), Santiago de Compostela, Spain; Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain; Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain
ISSN: 09646906





HUMAN MOLECULAR GENETICS
Editorial
OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND, Reino Unido
Tipo de documento: Article
Volumen: 31 Número: 22
Páginas: 3789-3806
WOS Id: 000840360300001
ID de PubMed: 35708486
imagen Green Published, hybrid

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