Detailed stratified GWAS analysis for severe COVID-19 in four European populations-Reference-Cited by-同舟云学术

Detailed stratified GWAS analysis for severe COVID-19 in four European populations

Published:2022-07-15 Issue:23 Volume:31 Page:3945-3966
ISSN:0964-6906
Container-title:Human Molecular Genetics
language:en
Short-container-title:

Author:

Degenhardt Frauke¹^ORCID,Ellinghaus David¹²,Juzenas Simonas¹³,Lerga-Jaso Jon⁴,Wendorff Mareike¹,Maya-Miles Douglas⁵⁶⁷,Uellendahl-Werth Florian¹,ElAbd Hesham¹,Rühlemann Malte C¹⁸,Arora Jatin⁹¹⁰¹¹¹²¹³¹⁴¹⁵,Özer Onur¹⁶¹⁷¹⁸,Lenning Ole Bernt¹⁹²⁰,Myhre Ronny²¹²²,Vadla May Sissel²⁰²³,Wacker Eike M¹,Wienbrandt Lars¹,Blandino Ortiz Aaron²⁴,de Salazar Adolfo²⁵²⁶,Garrido Chercoles Adolfo²⁷,Palom Adriana²⁸²⁹³⁰,Ruiz Agustín³¹³²,Garcia-Fernandez Alba-Estela³³,Blanco-Grau Albert³³,Mantovani Alberto³⁴³⁵,Zanella Alberto³⁶³⁷,Holten Aleksander Rygh³⁸³⁹,Mayer Alena⁴⁰,Bandera Alessandra³⁶³⁷,Cherubini Alessandro³⁷,Protti Alessandro³⁴³⁵,Aghemo Alessio³⁴³⁵,Gerussi Alessio⁴¹⁴²,Ramirez Alfredo⁴³⁴⁴⁴⁵⁴⁶⁴⁷⁴⁸,Braun Alice⁴⁰,Nebel Almut¹,Barreira Ana²⁹³⁰,Lleo Ana³⁴³⁵,Teles Ana¹⁶¹⁷¹⁸,Kildal Anders Benjamin⁴⁹^ORCID,Biondi Andrea⁵⁰,Caballero-Garralda Andrea⁵¹,Ganna Andrea⁵²,Gori Andrea³⁷⁵³,Glück Andreas⁵⁴,Lind Andreas⁵⁵,Tanck Anja¹,Hinney Anke⁵⁶,Carreras Nolla Anna⁵⁷,Fracanzani Anna Ludovica³⁶³⁷,Peschuck Anna¹,Cavallero Annalisa⁵⁸,Dyrhol-Riise Anne Ma³⁹⁵⁹,Ruello Antonella⁶⁰,Julià Antonio²⁸^ORCID,Muscatello Antonio³⁷,Pesenti Antonio³⁶³⁷,Voza Antonio³⁴³⁵,Rando-Segura Ariadna⁶¹⁶²,Solier Aurora⁶³⁶⁴,Schmidt Axel⁶⁵,Cortes Beatriz⁵⁷,Mateos Beatriz⁶⁶⁶,Nafria-Jimenez Beatriz²⁷,Schaefer Benedikt⁶⁷⁶⁸⁶⁹,Jensen Björn⁷⁰⁷¹,Bellinghausen Carla⁷²,Maj Carlo⁷³,Ferrando Carlos⁷⁴⁷⁵,de la Horra Carmen⁵⁷⁷⁶⁷⁷⁷⁸,Quereda Carmen⁷⁹,Skurk Carsten⁴⁰,Thibeault Charlotte⁴⁰,Scollo Chiara⁸⁰,Herr Christian⁸¹⁸²,Spinner Christoph D⁸³,Gassner Christoph¹⁸⁴,Lange Christoph⁸⁵⁸⁶⁸⁷,Hu Cinzia³⁷,Paccapelo Cinzia³⁷,Lehmann Clara⁸⁸⁸⁹⁹⁰,Angelini Claudio⁹¹,Cappadona Claudio³⁵,Azuure Clinton¹⁶¹⁷¹⁸,Bianco Cristiana³⁷,Cea Cristina³³,Sancho Cristina⁹²,Hoff Dag Arne Lihaug⁹³⁹⁴,Galimberti Daniela³⁶³⁷,Prati Daniele³⁷,Haschka David⁹⁵,Jiménez David⁶³⁶⁴,Pestaña David⁹⁶,Toapanta David⁷⁵,Muñiz-Diaz Eduardo⁹⁷,Azzolini Elena³⁴³⁵,Sandoval Elena⁷⁵,Binatti Eleonora⁴¹⁴²,Scarpini Elio³⁶³⁷,Helbig Elisa T⁴⁰,Casalone Elisabetta⁹⁸,Urrechaga Eloisa⁹⁹¹⁰⁰,Paraboschi Elvezia Maria³⁴³⁵^ORCID,Pontali Emanuele¹⁰¹,Reverter Enric⁷⁵,Calderón Enrique J⁵⁷⁷⁶⁷⁷⁷⁸,Navas Enrique⁷⁹,Solligård Erik¹⁰²¹⁰³,Contro Ernesto¹⁰⁴,Arana-Arri Eunate¹⁰⁰,Aziz Fátima⁷⁵,Garcia Federico²⁵²⁶¹⁰⁵,García Sánchez Félix¹⁰⁶,Ceriotti Ferruccio³⁷,Martinelli-Boneschi Filippo¹⁰⁷¹⁰⁸,Peyvandi Flora¹⁰⁹¹¹⁰,Kurth Florian⁴⁰¹¹¹¹¹²,Blasi Francesco¹¹³¹¹⁴,Malvestiti Francesco³⁶,Medrano Francisco J⁷⁷⁶⁷⁷⁷⁸¹¹⁵,Mesonero Francisco⁶⁶⁶,Rodriguez-Frias Francisco⁶²⁸³³⁶¹⁶²¹¹⁶,Hanses Frank¹¹⁷¹¹⁸,Müller Fredrik³⁹⁵⁵,Hemmrich-Stanisak Georg¹,Bellani Giacomo¹¹⁹¹²⁰¹²¹,Grasselli Giacomo³⁶³⁷,Pezzoli Gianni¹²²,Costantino Giorgio³⁶³⁷,Albano Giovanni⁶⁰,Cardamone Giulia³⁵,Bellelli Giuseppe¹²¹¹²³,Citerio Giuseppe¹²¹¹²⁴,Foti Giuseppe¹¹⁹¹²⁰¹²¹,Lamorte Giuseppe³⁷,Matullo Giuseppe⁹⁸,Baselli Guido³⁷,Kurihara Hayato⁹¹,Neb Holger¹²⁵¹²⁶,My Ilaria³⁴,Kurth Ingo¹²⁷,Hernández Isabel³¹³²,Pink Isabell¹²⁸,de Rojas Itziar³¹³²,Galván-Femenia Iván⁵⁷,Holter Jan Cato³⁹⁵⁵,Afset Jan Egil⁹²¹²⁹,Heyckendorf Jan⁸⁵⁸⁶⁸⁷,Kässens Jan¹,Damås Jan Kristian¹³⁰¹³¹,Rybniker Jan⁸⁸⁸⁹¹³²,Altmüller Janine¹³³,Ampuero Javier⁵⁶⁷⁷⁶¹³⁴,Martín Javier¹³⁵,Erdmann Jeanette¹³⁶¹³⁷¹³⁸,Banales Jesus M⁶¹³⁹¹⁴⁰,Badia Joan Ramon¹⁴¹,Dopazo Joaquin⁷¹⁴²^ORCID,Schneider Jochen⁸¹⁸²,Bergan Jonas¹⁴³,Barretina Jordi¹⁴⁴,Walter Jörn¹⁴⁵,Hernández Quero Jose²⁵¹⁴⁶,Goikoetxea Josune¹⁴⁷,Delgado Juan⁵⁷⁷⁶⁷⁷⁷⁸,Guerrero Juan M⁵⁷⁷⁶,Fazaal Julia⁶⁵,Kraft Julia⁴⁰,Schröder Julia⁶⁵,Risnes Kari¹³¹¹⁴⁸,Banasik Karina²,Müller Karl Erik¹⁴⁹,Gaede Karoline I¹⁵⁰¹⁵¹¹⁵²,Garcia-Etxebarria Koldo⁶¹³⁹,Tonby Kristian³⁹⁵⁹,Heggelund Lars¹⁴⁹¹⁵³,Izquierdo-Sanchez Laura⁶¹³⁹¹⁵⁴,Bettini Laura Rachele⁵⁰,Sumoy Lauro¹⁴⁴,Sander Leif Erik⁴⁰,Lippert Lena J⁴⁰,Terranova Leonardo³⁷,Nkambule Lindokuhle¹⁵⁵¹⁵⁶,Knopp Lisa⁷⁰⁷¹,Gustad Lise Tuset¹⁰²¹⁵⁷,Garbarino Lucia¹⁵⁸,Santoro Luigi³⁷,Téllez Luis⁶⁶⁶,Roade Luisa⁶²⁹³⁰⁶³,Ostadreza Mahnoosh³⁷,Intxausti Maider⁹²,Kogevinas Manolis⁷⁷¹⁵⁹¹⁶⁰¹⁶¹,Riveiro-Barciela Mar⁶²⁹³⁰⁶²,Berger Marc M¹⁶²,Schaefer Marco¹⁶³,Niemi Mari E K⁵²,Gutiérrez-Stampa María A¹⁶⁴¹⁶⁵,Carrabba Maria¹⁶⁶,Figuera Basso Maria E¹,Valsecchi Maria Grazia¹⁶⁷,Hernandez-Tejero María⁷⁵,Vehreschild Maria J G T¹⁶⁸¹⁶⁹,Manunta Maria³⁷^ORCID,Acosta-Herrera Marialbert¹³⁵^ORCID,D'Angiò Mariella⁵⁰,Baldini Marina³⁷,Cazzaniga Marina¹⁷⁰,Grimsrud Marit M³⁹¹⁷¹¹⁷²¹⁷³¹⁷⁴,Cornberg Markus¹⁷⁵¹⁷⁶,Nöthen Markus M⁶⁵,Marquié Marta³¹³²^ORCID,Castoldi Massimo⁶⁰,Cordioli Mattia⁵²,Cecconi Maurizio³⁴³⁵,D'Amato Mauro¹⁴⁰¹⁷⁷¹⁷⁸,Augustin Max⁸⁸⁸⁹⁹⁰,Tomasi Melissa³⁷,Boada Mercè³¹³²,Dreher Michael¹⁷⁹,Seilmaier Michael J¹⁸⁰,Joannidis Michael¹⁸¹¹⁸²,Wittig Michael¹,Mazzocco Michela¹⁵⁸,Ciccarelli Michele⁹¹,Rodríguez-Gandía Miguel⁶⁶⁶,Bocciolone Monica⁹¹,Miozzo Monica³⁶¹⁶⁶,Imaz Ayo Natale¹⁰⁰,Blay Natalia⁵⁷^ORCID,Chueca Natalia²⁶,Montano Nicola³⁶³⁷,Braun Nicole¹¹⁸³,Ludwig Nicole¹⁸⁴,Marx Nikolaus¹⁸⁵,Martínez Nilda¹⁸⁶,Cornely Oliver A⁴⁶⁸⁸⁹⁰¹⁸⁷,Witzke Oliver¹⁸⁸,Palmieri Orazio¹⁸⁹,Faverio Paola¹²¹¹⁹⁰,Preatoni Paoletta⁹¹,Bonfanti Paolo¹²¹¹⁹¹,Omodei Paolo⁹¹,Tentorio Paolo³⁴,Castro Pedro⁷⁵,Rodrigues Pedro M⁶¹³⁹¹⁴⁰¹⁵⁴,España Pedro Pablo⁹⁹,Hoffmann Per⁶⁵,Rosenstiel Philip¹,Schommers Philipp⁸⁸⁸⁹⁹⁰,Suwalski Phillip⁴⁰,de Pablo Raúl²⁴,Ferrer Ricard¹⁹²,Bals Robert⁸¹⁸²,Gualtierotti Roberta³⁶³⁷,Gallego-Durán Rocío⁵⁶⁷,Nieto Rosa⁶³⁶⁴,Carpani Rossana³⁷,Morilla Rubén⁵⁷⁷⁶⁷⁷⁷⁸,Badalamenti Salvatore³⁴,Haider Sammra¹⁹³,Ciesek Sandra¹⁹⁴¹⁹⁵,May Sandra¹,Bombace Sara³⁴³⁵,Marsal Sara²⁸,Pigazzini Sara⁵²,Klein Sebastian¹⁸¹¹⁸²,Pelusi Serena³⁶³⁷,Wilfling Sibylle¹¹⁸¹⁹⁶¹⁹⁷¹⁹⁸,Bosari Silvano³⁶³⁷,Volland Sonja¹⁹⁹,Brunak Søren²,Raychaudhuri Soumya⁹¹⁰¹¹¹²¹³¹⁴¹⁵²⁰⁰,Schreiber Stefan¹⁵⁴,Heilmann-Heimbach Stefanie⁶⁵,Aliberti Stefano³⁴³⁵,Ripke Stephan⁴⁰,Dudman Susanne³⁹⁵⁵^ORCID,Wesse Tanja¹,Zheng Tenghao²⁰¹,Bahmer Thomas⁵⁴,Eggermann Thomas¹²⁷,Illig Thomas¹⁹⁹,Brenner Thorsten¹⁶²,Pumarola Tomas²⁰²²⁰³,Feldt Torsten⁷⁰⁷¹,Folseraas Trine³⁹¹⁷¹¹⁷²¹⁷³¹⁷⁴²⁰⁴²⁰⁵,Gonzalez Cejudo Trinidad²⁰⁶,Landmesser Ulf²⁰⁷,Protzer Ulrike²⁰⁸²⁰⁹,Hehr Ute¹⁹⁶,Rimoldi Valeria³⁵,Monzani Valter³⁷,Skogen Vegard²¹⁰²¹¹,Keitel Verena⁷⁰⁷¹,Kopfnagel Verena¹⁹⁹,Friaza Vicente⁵⁷⁷⁶⁷⁷⁷⁸,Andrade Victor⁴³⁴⁴⁴⁵,Moreno Victor⁷⁷²¹²²¹³²¹⁴,Albrecht Wolfgang¹,Peter Wolfgang¹⁶³²¹⁵,Poller Wolfgang⁴⁰,Farre Xavier⁵⁷,Yi Xiaoli¹,Wang Xiaomin⁴⁰,Khodamoradi Yascha¹⁶⁸¹⁶⁹,Karadeniz Zehra⁴⁰,Latiano Anna¹⁸⁹,Goerg Siegfried²¹⁶,Bacher Petra¹²¹⁷,Koehler Philipp⁴⁶⁸⁸⁸⁹,Tran Florian¹⁵⁴,Zoller Heinz²¹⁸⁶⁹,Schulte Eva C²⁰⁸²¹⁹²²⁰,Heidecker Bettina⁴⁰,Ludwig Kerstin U⁶⁵^ORCID,Fernández Javier⁷⁵²²¹,Romero-Gómez Manuel⁵⁶⁷⁷⁶¹³⁴,Albillos Agustín⁶⁶⁶,Invernizzi Pietro⁴¹⁴²,Buti Maria⁶²⁹³⁰⁶²,Duga Stefano³⁴³⁵,Bujanda Luis⁶¹³⁹,Hov Johannes R³⁹¹⁷¹¹⁷²¹⁷³¹⁷⁴²⁰⁴²⁰⁵,Lenz Tobias L¹⁶¹⁷¹⁸,Asselta Rosanna³⁴³⁵,de Cid Rafael⁵⁷,Valenti Luca³⁶³⁷,Karlsen Tom H³⁹¹⁷¹¹⁷²¹⁷³¹⁷⁴²⁰⁴²⁰⁵,Cáceres Mario⁴²²²,Franke Andre¹²²³, , , ,

Affiliation:

1. Institute of Clinical Molecular Biology, Christian-Albrechts-University , Kiel , Germany

2. Novo Nordisk Foundation Center for Protein Research, Disease Systems Biology, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , Denmark

3. Life Science Centre, Institute of Biotechnology, Vilnius University , Vilnius , Lithuania

4. Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona , Barcelona , Spain

5. Hospital Universitario Virgen del Rocío de Sevilla , Sevilla , Spain

6. Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III (ISCIII) , Madrid , Spain

7. Instituto de Biomedicina de Sevilla (IBIS) , Sevilla , Spain

8. Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School , Hannover , Germany

9. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard , Cambridge, MA , USA

10. Division of Rheumatology , Inflammation and Immunity, , Boston, MA , USA

11. Brigham and Women’s Hospital and Harvard Medical School , Inflammation and Immunity, , Boston, MA , USA

12. Division of Genetics , Department of Medicine, , Boston, MA , USA

13. Brigham and Women’s Hospital , Department of Medicine, , Boston, MA , USA

14. Department of Biomedical Informatics, Harvard Medical School , Boston, MA , USA

15. Center for Data Sciences, Brigham and Women’s Hospital , Boston, MA , USA

16. Research Group for Evolutionary Immunogenomics, Max Planck Institute for Evolutionary Biology , Plön , Germany

17. Research Unit for Evolutionary Immunogenomics , Department of Biology, , Hamburg , Germany

18. University of Hamburg , Department of Biology, , Hamburg , Germany

19. Research Department, Stavanger University Hospital , Stavanger , Norway

20. Randaberg Municipality , Stavanger , Norway

21. Division of Health Data and Digitalization , Department of Genetics and Bioinformatics (HDGB), , Oslo , Norway

22. Norwegian Institute of Public Health , Department of Genetics and Bioinformatics (HDGB), , Oslo , Norway

23. Department of Quality and Health Technology, Faculty of Health Sciences, University of Stavanger , Stavanger , Norway

24. Department of Intensive Care, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), University of Alcalá , Madrid , Spain

25. Ibs.Granada Instituto de Investigación Biosanitaria , Granada , Spain

26. Microbiology Unit. Hospital Universitario Clinico San Cecilio , Granada , Spain

27. Clinical Biochemistry Department, Osakidetza Basque Health Service, Donostialdea Integrated Health Organisation , San Sebastian , Spain

28. Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari , Barcelona , Spain

29. Liver Unit , Department of Internal Medicine, , Barcelona , Spain

30. Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus , Department of Internal Medicine, , Barcelona , Spain

31. Research Center and Memory Clinic, Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya , Barcelona , Spain

32. CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III , Madrid , Spain

33. Department of Biochemistry, University Hospital Vall d’Hebron , Barcelona , Spain

34. IRCCS Humanitas Research Hospital , Milan , Italy

35. Department of Biomedical Sciences, Humanitas University , Milan , Italy

36. University of Milan , Milan , Italy

37. Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Milan , Italy

38. Department of Acute Medicine, Oslo University Hospital , Oslo , Norway

39. Institute of Clinical Medicine, University of Oslo , Oslo , Norway

40. Charite Universitätsmedizin Berlin , Berlin , Germany

41. European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital , Monza , Italy

42. Division of Gastroenterology, School of Medicine and Surgery, Center for Autoimmune Liver Diseases, University of Milano-Bicocca , Milan , Italy

43. Division of Neurogenetics and Molecular Psychiatry , Department of Psychiatry and Psychotherapy, , Cologne , Germany

44. Faculty of Medicine and University Hospital Cologne, University of Cologne , Department of Psychiatry and Psychotherapy, , Cologne , Germany

45. Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Medical Faculty , Bonn , Germany

46. Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Faculty of Medicine and University Hospital Cologne, University of Cologne , Cologne , Germany

47. German Center for Neurodegenerative Diseases (DZNE) , Bonn , Germany

48. Department of Psychiatry, Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases , San Antonio, TX , USA

49. Department of Anesthesiology and Intensive Care, University Hospital of North Norway , Tromsø , Norway

50. Pediatric Departement, Centro Tettamanti-European Reference Network (ERN) PaedCan, EuroBloodNet, MetabERN-University of Milano-Bicocca-Fondazione MBBM/Ospedale , San Gerardo , Italy

51. Biochemistry Department, Echevarne Laboratory , Barcelona , Spain

52. Institute for Molecular Medicine Finland, University of Helsinki , Helsinki , Finland

53. Centre for Multidisciplinary Research in Health Science (MACH), University of Milan , Milan , Italy

54. Klinik für Innere Medizin I, Universitätsklinikum Schleswig-Holstein , Kiel , Germany

55. Department of Microbiology, Oslo University Hospital , Oslo , Norway

56. Department of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen , Essen , Germany

57. Genomes for Life-GCAT Lab, Germans Trias i Pujol Research Institute (IGTP) , Badalona , Spain

58. Laboratory of Microbiology, San Gerardo Hospital , Monza , Italy

59. Department of Infectious diseases, Oslo University Hospital , Oslo , Norway

60. Humanitas Gavazzeni-Castelli , Bergamo , Italy

61. Microbiology Department, Hospital Universitari Vall d'Hebron , Barcelona , Spain

62. Universitat Autònoma de Barcelona , Bellatera , Spain

63. Department of Respiratory Diseases, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), University of Alcalá , Madrid , Spain

64. Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), University of Alcalá , Madrid , Spain

65. Institute of Human Genetics, University of Bonn School of Medicine & University Hospital Bonn , Bonn , Germany

66. Department of Gastroenterology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), University of Alcalá , Madrid , Spain

67. Department of Medicine I , Gastroenterology, Hepatology and Endocrinology, , Innsbruck , Austria

68. Medical University of Innsbruck , Gastroenterology, Hepatology and Endocrinology, , Innsbruck , Austria

69. Christian Doppler Laboratory of Iron and Phosphate Biology at the Department of Medicine I, Medical University of Innsbruck , Innsbruck , Austria

70. Department of Gastroenterology , Hepatology and Infectious Diseases, , Duesseldorf , Germany

71. University Hospital Duesseldorf, Medical Faculty Heinrich Heine University , Hepatology and Infectious Diseases, , Duesseldorf , Germany

72. Department of Respiratory Medicine and Allergology, University Hospital, Goethe University , Frankfurt am Main , Germany

73. Institute of Genomic Statistics and Bioinformatics, University Hospital Bonn, Medical Faculty University of Bonn , Bonn , Germany

74. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES) , Madrid , Spain

75. Hospital Clinic, University of Barcelona, and IDIBAPS , Barcelona , Spain

76. University of Sevilla , Sevilla , Spain

77. Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP) , Madrid , Spain

78. Consejo Superior de Investigaciones Científicas , Sevilla , Spain

79. Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), University of Alcalá , Madrid , Spain

80. Department of Transfusion Medicine and Haematology Laboratory, San Gerardo Hospital , Monza , Italy

81. Department of Internal Medicine V—Pneumology , Allergology and Intensive Care Medicine, , Homburg , Germany

82. University Hospital Saarland , Allergology and Intensive Care Medicine, , Homburg , Germany

83. Department of Internal Medicine II, School of Medicine, University Hospital rechts der Isar, Technical University of Munich , Munich , Germany

84. Institute of Translational Medicine, Private University in the Principality of Liechtenstein (UFL) , Triesen , Liechtenstein

85. Respiratory Medicine and International Health, University of Lübeck , Lübeck , Germany

86. Division of Clinical Infectious Diseases, Research Center Borstel , Borstel , Germany

87. Clinical Tuberculosis Unit, German Center for Infection Research (DZIF) , Borstel , Germany

88. Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne , Cologne , Germany

89. Center for Molecular Medicine Cologne (CMMC), University of Cologne , Cologne , Germany

90. German Center for Infection Research (DZIF) , Cologne , Germany

91. Humanitas Clinical and Research Center, IRCCS , Milan , Italy

92. Osakidetza Basque Health Service, Basurto University Hospital, Respiratory Service , Bilbao , Spain

93. Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology , Trondheim , Norway

94. Department of Medicine, Møre and Romsdal Hospital Trust , Ålesund , Norway

95. Department of Internal Medicine II, Medical University of Innsbruck , Innsbruck , Austria

96. Department of Anesthesiology and Critical Care, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), University of Alcalá , Madrid , Spain

97. Immunohematology Department, Banc de Sang i Teixits, Autonomous University of Barcelona , Barcelona , Spain

98. Department of Medical Sciences, Università degli Studi di Torino , Turin , Italy

99. Osakidetza Basque Health Service, Galdakao Hospital, Respiratory Service , Galdakao , Spain

100. Biocruces Bizkaia Health Research Institute , Barakaldo , Spain

101. Department of Infectious Diseases, E.O. Ospedali Galliera , Genova , Italy

102. Geminicenter for Sepsis Research, Institute of Circulation and Medical Imaging (ISB), NTNU , Trondheim , Norway

103. Clinic of Anesthesia and Intensive Care, St. Olavs Hospital, Trondheim University Hospital , Trondheim , Norway

104. Accident and Emergency and Emergency Medicine Unit, San Gerardo Hospital , Monza , Italy

105. Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII) , Madrid , Spain

106. Histocompatibilidad y Biologia Molecular, Centro de Transfusion de Madrid , Madrid , Spain

107. Department of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan , Milan , Italy

108. Neurology Unit, IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico , Milan , Italy

109. Department of Pathophysiology and Transplantation, University of Milan , Milan , Italy

110. Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center , Milan , Italy

111. Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine , Hamburg , Germany

112. Department of Medicine I, University Medical Centre Hamburg-Eppendorf , Hamburg , Germany

113. Respiratory Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Milan , Italy

114. Department of Pathophysiology and Transplantation, Università degli Studi di Milano , Milan , Italy

115. Internal Medicine Department, Virgen del Rocio University Hospital , Sevilla , Spain

116. Biochemistry Department, University Hospital Vall d'Hebron , Barcelona , Spain

117. Emergency Department, University Hospital Regensburg , Regensburg , Germany

118. Department for Infectious Diseases and Infection Control, University Hospital Regensburg , Regensburg , Germany

119. Department Emergency , Anesthesia and Intensive Care, , Monza , Italy

120. San Gerardo Hospital , Anesthesia and Intensive Care, , Monza , Italy

121. School of Medicine and Surgery, University of Milano-Bicocca , Milan , Italy

122. Fondazione Grigioni per il Morbo di Parkinson and Parkinson Institute, ASST Gaetano Pini-CTO , Milan , Italy

123. Acute Geriatric Unit, San Gerardo Hospital , Monza , Italy

124. Neurointensive Care Unit, San Gerardo Hospital , Monza , Italy

125. Department of Anesthesiology , Intensive Care Medicine and Pain Therapy, , Frankfurt am Main , Germany

126. University Hospital Frankfurt , Intensive Care Medicine and Pain Therapy, , Frankfurt am Main , Germany

127. Institute of Human Genetics, Medical Faculty, RWTH Aachen University , Aachen , Germany

128. Department of Pneumology, Hannover Medical School , Hannover , Germany

129. Department of Medical Microbiology, Clinic of Laboratory Medicine, St. Olavs hospital , Trondheim , Norway

130. Department of Infectious Diseases, St. Olavs Hospital, Trondheim University Hospital , Trondheim , Norway

131. Department of Clinical and Molecular Medicine, NTNU , Trondheim , Norway

132. German Centre for Infection Research (DZIF) , Cologne , Germany

133. Cologne Center for Genomics (CCG), University of Cologne , Cologne , Germany

134. Digestive Diseases Unit, Virgen del Rocio University Hospital, Institute of Biomedicine of Seville, University of Seville , Seville , Spain

135. Institute of Parasitology and Biomedicine Lopez-Neyra , CSIC, Granada , Spain

136. Institute for Cardiogenetics, University of Lübeck , Lübeck , Germany

137. German Research Center for Cardiovascular Research , Lübeck , Germany

138. University Heart Center Lübeck , Lübeck , Germany

139. Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute—Donostia University Hospital, University of the Basque Country (UPV/EHU), CIBERehd, Ikerbasque , San Sebastian , Spain

140. Ikerbasque, Basque Foundation for Science , Bilbao , Spain

141. Respiratory ICU, Institut Clínic Respiratory, Hospital Clinic, University of Barcelona, and IDIBAPS , Barcelona , Spain

142. Bioinformatics Area, Fundación Progreso y Salud, and Institute of Biomedicine of Sevilla (IBIS) , Sevilla , Spain

143. Department of Research, Ostfold Hospital Trust , Gralum , Norway

144. Germans Trias i Pujol Research Institute (IGTP) , Badalona , Spain

145. Department of Genetics & Epigenetics, Saarland University , Saarbrücken , Germany

146. Department of Infectious Diseases, Hospital Universitario Clinico San Cecilio , Granada , Spain

147. Infectious Diseases Service, Osakidetza, Biocruces Bizkaia Health Research Institute , Barakaldo , Spain

148. Department of Research, St. Olav Hospital, Trondheim University Hospital , Trondheim , Norway

149. Medical Department, Drammen Hospital, Vestre Viken Hospital Trust , Drammen , Norway

150. Research Center Borstel, BioMaterialBank Nord , Borstel , Germany

151. German Center for Lung Research (DZL), Airway Research Center North (ARCN) , Borstel , Germany

152. Popgen 2.0 Network (P2N) , Kiel , Germany

153. Department of Clinical Science, University of Bergen , Bergen , Norway

154. Biodonostia Health Research Institute, Donostia University Hospital , San Sebastian , Spain

155. Analytic and Translational Genetics Unit, Massachusetts General Hospital , Boston, MA , USA

156. Stanley Center for Psychiatric Research & Program in Medical and Population Genetics, Broad Institute of MIT and Harvard , Cambridge, MA , USA

157. Clinic of Medicine and Rehabilitation, Levanger Hospital, Nord-Trondelag Hospital Trust , Levanger , Norway

158. HLA Laboratory, E.O. Ospedali Galliera , Genova , Italy

159. ISGlobal , Barcelona , Spain

160. Universitat Pompeu Fabra (UPF) , Barcelona , Spain

161. IMIM (Hospital del Mar Medical Research Institute) , Barcelona , Spain

162. Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen , Essen , Germany

163. Stefan-Morsch-Stiftung , Birkenfeld , Germany

164. Osakidetza , OSI Donostialdea, Altza Primary Care, , San Sebastián , Spain

165. Biodonostia Health Research Institute , OSI Donostialdea, Altza Primary Care, , San Sebastián , Spain

166. Internal Medicine Department, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico , Milan , Italy

167. Center of Bioinformatics, Biostatistics and Bioimaging, School of Medicine and Surgery, University of Milano-Bicocca , Milan , Italy

168. Department of Internal Medicine , Infectious Diseases, , Frankfurt am Main , Germany

169. University Hospital Frankfurt & Goethe University Frankfurt , Infectious Diseases, , Frankfurt am Main , Germany

170. Phase 1 Research Centre, ASST Monza, School of Medicine and Surgery, University of Milano-Bicocca , Monza , Italy

171. Division of Surgery , Inflammatory Diseases and Transplantation, , Oslo , Norway

172. Research Institute for Internal Medicine, Oslo University Hospital Rikshospitalet and University of Oslo , Inflammatory Diseases and Transplantation, , Oslo , Norway

173. Division of Surgery , Inflammatory Diseases and Transplantation, Department of Transplantation Medicine, , Oslo , Norway

174. Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet , Inflammatory Diseases and Transplantation, Department of Transplantation Medicine, , Oslo , Norway

175. Department of Gastroenterology , Hepatology and Endocrinology, , Hannover , Germany

176. Hannover Medical School , Hepatology and Endocrinology, , Hannover , Germany

177. Gastrointestinal Genetics Lab, CIC bioGUNE—BRTA , Derio , Spain

178. Department of Medicine and Surgery, LUM University , Casamassima , Italy

179. Department of Pneumology and Intensive Care Medicine, University Hospital Aachen , Aachen , Germany

180. Munich Clinic Schwabing, Academic Teaching Hospital, Ludwig-Maximilians-University (LMU) , Munich , Germany

181. Division of Intensive Care and Emergency Medicine , Department of Internal Medicine, , Innsbruck , Austria

182. Medical University Innsbruck , Department of Internal Medicine, , Innsbruck , Austria

183. University Hospital Schleswig-Holstein , Kiel , Germany

184. Department of Human Genetics, Center of Human and Molecular Biology, University Hospital Saarland , Homburg/Saar , Germany

185. Department of Internal Medicine I, RWTH Aachen University Hospital , Aachen , Germany

186. Department of Anesthesiology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) , Madrid , Spain

187. Faculty of Medicine and University Hospital Cologne , Clinical Trials Centre Cologne (ZKS Köln), University of Cologne, Cologne , Germany

188. Department of Infectious Diseases, University Hospital Essen, University Duisburg-Essen , Essen , Germany

189. Gastroenterology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza , San Giovanni Rotondo , Italy

190. Pulmonary Unit, San Gerardo Hospital , Monza , Italy

191. Infectious Diseases Unit, San Gerardo Hospital , Monza , Italy

192. Intensive Care Department, Vall d'Hebron University Hospital, SODIR-VHIR research group , Barcelona , Spain

193. Department of Medicine, Møre & Romsdal Hospital Trust , Molde , Norway

194. Institute of Medical Virology, University Hospital Frankfurt, Goethe University , Frankfurt am Main , Germany

195. German Centre for Infection Research (DZIF) , Frankfurt am Main , Germany

196. Zentrum für Humangenetik Regensburg , Regensburg , Germany

197. Department of Neurology , Bezirksklinikum Regensburg, , Regensburg , Germany

198. University of Regensburg , Bezirksklinikum Regensburg, , Regensburg , Germany

199. Hannover Unified Biobank, Hannover Medical School , Hannover , Germany

200. Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, The University of Manchester , Manchester , UK

201. School of Biological Sciences, Monash University , Clayton, VIC , Australia

202. Department of Microbiology, University Hospital Vall d’Hebron , Barcelona , Spain

203. Autonoma University of Barcelona , Barcelona , Spain

204. Division for Cancer Medicine , Surgery and Transplantation, Section for Gastroenterology, Department of Transplantation Medicine, , Oslo , Norway

205. Oslo University Hospital Rikshospitalet , Surgery and Transplantation, Section for Gastroenterology, Department of Transplantation Medicine, , Oslo , Norway

206. Biochemistry Unit, Hospital Universitario Clinico San Cecilio , Granada , Spain

207. Berlin Institute of Health, Charite Universitätsmedizin Berlin , Berlin Germany

208. Institute of Virology, Technical University Munich/Helmholtz Zentrum München , Munich , Germany

209. German Center for Infection Research (DZIF) , Munich , Germany

210. Department of Infectious Diseases, University Hospital of North Norway , Tromsø , Norway

211. Faculty of Health Sciences, UIT The Arctic University of Norway , Norway

212. Catalan Institute of Oncology (ICO) , Barcelona , Spain

213. Bellvitge Biomedical Research Institute (IDIBELL) , Barcelona , Spain

214. Universitat de Barcelona (UB) , Barcelona , Spain

215. Faculty of Medicine and University Hospital Cologne, Institute for Transfusion Medicine, University of Cologne , Cologne , Germany

216. Institute of Transfusionsmedicine, University Hospital Schleswig-Holstein (UKSH) , Kiel , Germany

217. Institute of Immunology, Christian-Albrechts-University of Kiel and UKSH Schleswig-Holstein , Kiel , Germany

218. Department of Medicine I, Gastroenterology, Hepatology and Endocrinology, Medical University of Innsbruck , Innsbruck , Austria

219. Institute of Psychiatric Phenomics and Genomics, University Medical Center, University of Munich , Munich , Germany

220. Department of Psychiatry, University Medical Center, University of Munich , Munich , Germany

221. European Foundation for the Study of Chronic Liver Failure (EF-CLIF) , Barcelona , Spain

222. ICREA , Barcelona , Spain

223. University Hospital Schleswig-Holstein (UKSH) , Kiel , Germany

Abstract

Abstract Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a ~0.9-Mb inversion polymorphism that creates two highly differentiated haplotypes and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative including non-Caucasian individuals, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.

Funder

Deutsche Forschungsgemeinschaft

Juan de la Cierva Incorporacion program

German Federal Ministry of Education and Research

Research Council of Norway

Spanish Ministry of Economy, Innovation and Competition, the Instituto de Salud Carlos III

Agencia Estatal de Investigación (AEI, Spain) and the European Regional Development Fund

Basque Foundation for Health Innovation and Research-BIOEF

Acción Estratégica en Salud (ISCIII) and the FEDER

Spanish Ministry of Economy and Competitiveness

European Regional Development Fund

VEIS project

Agència de Gestió d’Ajuts Universitaris i de Recerca

Acción de Dinamización del ISCIII-MINECO and the Ministry of Health of the Generalitat of Catalunya

Fondazione IRCCS Ca’ Granda ‘5permille’ ‘COVID-19 Biobank’

Fondazione IRCCS Ca’ Granda ‘Ricerca corrente’, Fondazione Sviluppo Ca’ Granda ‘Liver-BIBLE’

The European Union (EU) Programme Horizon 2020

Ricerca Finalizzata Ministero della Salute

German Research Foundation (DFG) through the Research Training Group

Novo Nordisk Foundation

German Federal Ministry of Education and Research (BMBF) within the framework of the Computational Life Sciences

Deutsche Forschungsgemeinschaft Cluster of Excellence ‘Precision Medicine in Chronic Inflammation’

Publisher

Oxford University Press (OUP)

Subject

Genetics (clinical),Genetics,Molecular Biology,General Medicine

Link

https://academic.oup.com/hmg/advance-article-pdf/doi/10.1093/hmg/ddac158/45905823/ddac158.pdf

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