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

Author

Medicina, Medikuntza, Goikoetxea Agirre, Ane Josune, COVICAT Study Group, Aachen Study (COVAS), Norwegian SARS CoV-2 Study Group, Pa Study Group, STORM Study Group, The Humanitas Task Force, The Humanitas Gavazzeni Task Force, Medicina, Medikuntza, Goikoetxea Agirre, Ane Josune, COVICAT Study Group, Aachen Study (COVAS), Norwegian SARS CoV-2 Study Group, Pa Study Group, STORM Study Group, The Humanitas Task Force, and The Humanitas Gavazzeni Task Force

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 12488 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.

Published
2022

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

Author

Federal Ministry of Education and Research (Germany), German Research Foundation, Novo Nordisk Foundation, Ministero della Salute, European Commission, Fondazione Cariplo, Ministero dell'Istruzione, dell'Università e della Ricerca, Generalitat de Catalunya, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Fundación la Caixa, Eusko Jaurlaritza, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Junta de Andalucía, Centro de Investigación Biomédica en Red Epidemiología y Salud Pública (España), Norwegian Research Council, German Center for Lung Research, Airway Research Center North (Germany), Miltenyi Biotec, University of Cologne, Technical University of Munich, Finnish Institute for Molecular Medicine, University of Helsinki, Saarland University, University Hospital Bonn, Bavarian State Ministry of Education, Science and the Arts, Essen University Hospital, Degenhardt, Frauke, Ellinghaus, David, Juzenas, Simonas, Lerga-Jaso, Jon, Wendorff, Mareike, Maya-Miles, Douglas, Uellendahl-Werth, Florian, ElAbd, Hesham, Rühlemann, Malte C., Arora, Jatin, Özer, Onur, Salazar, Adolfo de, Risnes, Kari, Banasik, Karina, Müller, Karl Erik, Gaede, Karoline I., Pigazzini, Sara, García-Etxebarria, Koldo, Tonby, Kristian, Heggelund, Lars, Asselta, Rosanna, Sancho, Cristina, Ruiz, Agustín, Izquierdo-Sanchez, Laura, Rachele Bettini, Laura, Sumoy, Lauro, Garrido Chercoles, Adolfo, Sander, Leif Erik, Valsecchi, Maria Grazia, Klein, Sebastian, Hernández-Tejero, María, Vehreschild, Maria J. G. T., Lihaug Hoff, Dag Arne, Roade, Luisa, Manunta, Maria, Acosta-Herrera, Marialbert, D’Angiò, Mariella, Baldini, Marina, Cazzaniga, Marina, Grimsrud, Marit M., Urrechaga, Eloisa, Cornberg, Markus, Pelusi, Serena, Galimberti, Daniela, García-Fernández, Alba-Estela, Bals, Robert, Nöthen, Markus M., Marquié, Marta, Castoldi, Massimo, Cordioli, Mattia, Cecconi, Maurizio, D’Amato, Mauro, Augustin, Max, Tomasi, Melissa, Prati, Daniele, Paraboschi, Elvezia Maria, Bandera, Alessandra, Braun, Alice, Boada, Mercè, Dreher, Michael, Blanco-Grau, Albert, Seilmaier, Michael J., Joannidis, Michael, Wittig, Michael, Mazzocco, Michela, Haschka, David, Ciccarelli, Michele, Rodríguez-Gandía, Miguel, Bocciolone, Monica, Cid, Rafael de, Wilfling, Sibylle, Pontali, Emanuele, Miozzo, Monica, Imaz Ayo, Natale, Blay, Natalia, Mantovani, Alberto, Berger, Marc M., Chueca, Natalia, Montano, Nicola, Braun, Nicole, Ludwig, Nicole, Valenti, Luca, Marx, Nikolaus, Bosari, Silvano, Martínez, Nilda, Reverter, Enric, Norwegian SARS-CoV-2 Study group, Jiménez, David, Cornely, Oliver A., Witzke, Oliver, Palmieri, Orazio, Zanella, Alberto, Pa COVID-19 Study Group, Karlsen, Tom H., Faverio, Paola, Preatoni, Paoletta, Terranova, Leonardo, Bonfanti, Paolo, Pestaña, David, Omodei, Paolo, Calderón, Enrique J., Tentorio, Paolo, Castro Blázquez, Pedro, Rodrigues, Pedro M., España, Pedro Pablo, Cáceres, Mario, Hoffmann, Per, Holten, Aleksander Rygh, Rosenstiel, Philip, Toapanta, David, Contro, Ernesto, Schommers, Philipp, Suwalski, Phillip, Pablo, Raúl de, Navas, Enrique, Ferrer, Ricard, Volland, Sonja, Franke, Andre, Brunak, Søren, Raychaudhuri, Soumya, Haider, Sammra, Schreiber, Stefan, Heilmann-Heimbach, Stefanie, Aliberti, Stefano, Ripke, Stephan, Dudman, Susanne, Cherubini, Alessandro, Nkambule, Lindokuhle, Wesse, Tanja, Nebel, Almut, Lenning, Ole Bernt, Albillos, Agustín, Zheng, Tenghao, The Humanitas COVID-19 Task Force, The Humanitas Gavazzeni COVID-19 Task Force, Bahmer, Thomas, Eggermann, Thomas, Illig, Thomas, Brenner, Thorsten, Pumarola, Tomàs, Knopp, Lisa, Martinelli-Boneschi, Filippo, Medrano, Francisco Javier, Feldt, Torsten, Protti, Alessandro, Arana-Arri, Eunate, Folseraas, Trine, Gonzalez Cejudo, Trinidad, Landmesser, Ulf, Protzer, Ulrike, Hehr, Ute, Rimoldi, Valeria, Monzani, Valter, Muñiz-Diaz, Eduardo, Barreira, Ana, Gustad, Lise Tuset, Skogen, Vegard, Keitel, Verena, Kopfnagel, Verena, Aziz, Fátima, Aghemo, Alessio, Friaza Patiño, Vicente, Andrade, Victor, Moreno, Victor, Azzolini, Elena, Albrecht, Wolfgang, Lleo, Ana, Peter, Wolfgang, Garbarino, Lucia, Poller, Wolfgang, Farré, Xavier, Yi, Xiaoli, Wang, Xiaomin, García, Federico, Khodamoradi, Yascha, Sandoval, Elena, Gerussi, Alessio, Karadeniz, Zehra, Gualtierotti, Roberta, Latiano, Anna, Goerg, Siegfried, Santoro, Luigi, Bacher, Petra, Koehler, Philipp, Tran, Florian, Zoller, Heinz, Binatti, Eleonora, Schulte, Eva C., García Sánchez, Félix, Heidecker, Bettina, Palom, Adriana, Ludwig, Kerstin U., Ramírez, Alfredo, Fernández, Javier, Téllez, Luis, Romero-Gómez, Manuel, Teles, Ana, Scarpini, Elio, Kildal, Anders Benjamin, Biondi, Andrea, Caballero-Garralda, Andrea, Ganna, Andrea, Gori, Andrea, Glück, Andreas, Lind, Andreas, Peyvandi, Flora, Gallego-Durán, Rocío, Tanck, Anja, Mesonero, Francisco, Helbig, Elisa T., Hinney, Anke, Carreras Nolla, Anna, Fracanzani, Anna Ludovica, Peschuck, Anna, Cavallero, Annalisa, Dyrhol-Riise, Anne Ma, Ruello, Antonella, Julià, Antonio, Nieto, Rosa, Schaefer, Marco, Muscatello, Antonio, Kurth, Florian, Ostadreza, Mahnoosh, Pesenti, Antonio, Voza, Antonio, Rando-Segura, Ariadna, Solier-López, Aurora, Schmidt, Axel, Cortes, Beatriz, Mateos, Beatriz, Rodríguez-Frías, Francisco, Carpani, Rossana, Nafría-Jiménez, Beatriz, Schaefer, Benedikt, Jensen, Björn, Intxausti, Maider, Blasi, Francesco, Bellinghausen, Carla, Maj, Carlo, Ferrando, Carlos, Horra, Carmen de la, Hanses, Frank, Quereda, Carmen, Mayer, Alena, Skurk, Carsten, Thibeault, Charlotte, Scollo, Chiara, Herr, Christian, Kogevinas, Manolis, Spinner, Christoph D., Malvestiti, Francesco, Gassner, Christoph, Invernizzi, Pietro, Lange, Christoph, Hu, Cinzia, Morilla Romero de la Osa, R., Paccapelo, Cinzia, Lehmann, Clara, Angelini, Claudio, Cappadona, Claudio, Azuure, Clinton, Riveiro-Barciela, Mar, COVICAT study group, Solligård, Erik, Covid-19 Aachen Study (COVAS), Myhre, Ronny, Bianco, Cristiana, Badalamenti, Salvatore, Cea, Cristina, Müller, Fredrik, Hemmrich-Stanisak, Georg, Bellani, Giacomo, Grasselli, Giacomo, Pezzoli, Gianni, Costantino, Giorgio, Vadla, May Sissel, Albano, Giovanni, Niemi, Mari, Buti, María, Cardamone, Giulia, Lippert, Lena J., Bellelli, Giuseppe, Citerio, Giuseppe, Foti, Giuseppe, Lamorte, Giuseppe, Matullo, Giuseppe, Baselli, Guido, Kurihara, Hayato, Neb, Holger, Duga, Stefano, Wacker, Eike M., Gutiérrez-Stampa, María A., Ciesek, Sandra, My, Ilaria, Kurth, Ingo, Hernández, Isabel, Pink, Isabell, Rojas, Itziar de, Galván-Femenia, Iván, Holter, Jan Cato, Bujanda, Luis, Afset, Jan Egil, Heyckendorf, Jan, Kässens, Jan, May, Sandra, Carrabba, Maria, Wienbrandt, Lars, Damås, Jan Kristian, Rybniker, Jan, Altmüller, Janine, Ampuero, Javier, Ceriotti, Ferruccio, Martín, Javier, Erdmann, Jeanette, Banales, Jesús M., Badia, Joan Ramon, Bombace, Sara, Dopazo, Joaquín, Figuera Basso, Maria E., Schneider, Jochen, Blandino Ortiz, Aaron, Bergan, Jonas, Hov, Johannes R., Barretina, Jordi, Walter, Jörn, Hernández Quero, José, Goikoetxea-Aguirre, Josune, Delgado, Juan, Marsal, Sara, Guerrero, Juan M., Fazaal, Julia, Casalone, Elisabetta, Kraft, Julia, Lenz, Tobias L., Schröder, Julia, Federal Ministry of Education and Research (Germany), German Research Foundation, Novo Nordisk Foundation, Ministero della Salute, European Commission, Fondazione Cariplo, Ministero dell'Istruzione, dell'Università e della Ricerca, Generalitat de Catalunya, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Fundación la Caixa, Eusko Jaurlaritza, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Junta de Andalucía, Centro de Investigación Biomédica en Red Epidemiología y Salud Pública (España), Norwegian Research Council, German Center for Lung Research, Airway Research Center North (Germany), Miltenyi Biotec, University of Cologne, Technical University of Munich, Finnish Institute for Molecular Medicine, University of Helsinki, Saarland University, University Hospital Bonn, Bavarian State Ministry of Education, Science and the Arts, Essen University Hospital, Degenhardt, Frauke, Ellinghaus, David, Juzenas, Simonas, Lerga-Jaso, Jon, Wendorff, Mareike, Maya-Miles, Douglas, Uellendahl-Werth, Florian, ElAbd, Hesham, Rühlemann, Malte C., Arora, Jatin, Özer, Onur, Salazar, Adolfo de, Risnes, Kari, Banasik, Karina, Müller, Karl Erik, Gaede, Karoline I., Pigazzini, Sara, García-Etxebarria, Koldo, Tonby, Kristian, Heggelund, Lars, Asselta, Rosanna, Sancho, Cristina, Ruiz, Agustín, Izquierdo-Sanchez, Laura, Rachele Bettini, Laura, Sumoy, Lauro, Garrido Chercoles, Adolfo, Sander, Leif Erik, Valsecchi, Maria Grazia, Klein, Sebastian, Hernández-Tejero, María, Vehreschild, Maria J. G. T., Lihaug Hoff, Dag Arne, Roade, Luisa, Manunta, Maria, Acosta-Herrera, Marialbert, D’Angiò, Mariella, Baldini, Marina, Cazzaniga, Marina, Grimsrud, Marit M., Urrechaga, Eloisa, Cornberg, Markus, Pelusi, Serena, Galimberti, Daniela, García-Fernández, Alba-Estela, Bals, Robert, Nöthen, Markus M., Marquié, Marta, Castoldi, Massimo, Cordioli, Mattia, Cecconi, Maurizio, D’Amato, Mauro, Augustin, Max, Tomasi, Melissa, Prati, Daniele, Paraboschi, Elvezia Maria, Bandera, Alessandra, Braun, Alice, Boada, Mercè, Dreher, Michael, Blanco-Grau, Albert, Seilmaier, Michael J., Joannidis, Michael, Wittig, Michael, Mazzocco, Michela, Haschka, David, Ciccarelli, Michele, Rodríguez-Gandía, Miguel, Bocciolone, Monica, Cid, Rafael de, Wilfling, Sibylle, Pontali, Emanuele, Miozzo, Monica, Imaz Ayo, Natale, Blay, Natalia, Mantovani, Alberto, Berger, Marc M., Chueca, Natalia, Montano, Nicola, Braun, Nicole, Ludwig, Nicole, Valenti, Luca, Marx, Nikolaus, Bosari, Silvano, Martínez, Nilda, Reverter, Enric, Norwegian SARS-CoV-2 Study group, Jiménez, David, Cornely, Oliver A., Witzke, Oliver, Palmieri, Orazio, Zanella, Alberto, Pa COVID-19 Study Group, Karlsen, Tom H., Faverio, Paola, Preatoni, Paoletta, Terranova, Leonardo, Bonfanti, Paolo, Pestaña, David, Omodei, Paolo, Calderón, Enrique J., Tentorio, Paolo, Castro Blázquez, Pedro, Rodrigues, Pedro M., España, Pedro Pablo, Cáceres, Mario, Hoffmann, Per, Holten, Aleksander Rygh, Rosenstiel, Philip, Toapanta, David, Contro, Ernesto, Schommers, Philipp, Suwalski, Phillip, Pablo, Raúl de, Navas, Enrique, Ferrer, Ricard, Volland, Sonja, Franke, Andre, Brunak, Søren, Raychaudhuri, Soumya, Haider, Sammra, Schreiber, Stefan, Heilmann-Heimbach, Stefanie, Aliberti, Stefano, Ripke, Stephan, Dudman, Susanne, Cherubini, Alessandro, Nkambule, Lindokuhle, Wesse, Tanja, Nebel, Almut, Lenning, Ole Bernt, Albillos, Agustín, Zheng, Tenghao, The Humanitas COVID-19 Task Force, The Humanitas Gavazzeni COVID-19 Task Force, Bahmer, Thomas, Eggermann, Thomas, Illig, Thomas, Brenner, Thorsten, Pumarola, Tomàs, Knopp, Lisa, Martinelli-Boneschi, Filippo, Medrano, Francisco Javier, Feldt, Torsten, Protti, Alessandro, Arana-Arri, Eunate, Folseraas, Trine, Gonzalez Cejudo, Trinidad, Landmesser, Ulf, Protzer, Ulrike, Hehr, Ute, Rimoldi, Valeria, Monzani, Valter, Muñiz-Diaz, Eduardo, Barreira, Ana, Gustad, Lise Tuset, Skogen, Vegard, Keitel, Verena, Kopfnagel, Verena, Aziz, Fátima, Aghemo, Alessio, Friaza Patiño, Vicente, Andrade, Victor, Moreno, Victor, Azzolini, Elena, Albrecht, Wolfgang, Lleo, Ana, Peter, Wolfgang, Garbarino, Lucia, Poller, Wolfgang, Farré, Xavier, Yi, Xiaoli, Wang, Xiaomin, García, Federico, Khodamoradi, Yascha, Sandoval, Elena, Gerussi, Alessio, Karadeniz, Zehra, Gualtierotti, Roberta, Latiano, Anna, Goerg, Siegfried, Santoro, Luigi, Bacher, Petra, Koehler, Philipp, Tran, Florian, Zoller, Heinz, Binatti, Eleonora, Schulte, Eva C., García Sánchez, Félix, Heidecker, Bettina, Palom, Adriana, Ludwig, Kerstin U., Ramírez, Alfredo, Fernández, Javier, Téllez, Luis, Romero-Gómez, Manuel, Teles, Ana, Scarpini, Elio, Kildal, Anders Benjamin, Biondi, Andrea, Caballero-Garralda, Andrea, Ganna, Andrea, Gori, Andrea, Glück, Andreas, Lind, Andreas, Peyvandi, Flora, Gallego-Durán, Rocío, Tanck, Anja, Mesonero, Francisco, Helbig, Elisa T., Hinney, Anke, Carreras Nolla, Anna, Fracanzani, Anna Ludovica, Peschuck, Anna, Cavallero, Annalisa, Dyrhol-Riise, Anne Ma, Ruello, Antonella, Julià, Antonio, Nieto, Rosa, Schaefer, Marco, Muscatello, Antonio, Kurth, Florian, Ostadreza, Mahnoosh, Pesenti, Antonio, Voza, Antonio, Rando-Segura, Ariadna, Solier-López, Aurora, Schmidt, Axel, Cortes, Beatriz, Mateos, Beatriz, Rodríguez-Frías, Francisco, Carpani, Rossana, Nafría-Jiménez, Beatriz, Schaefer, Benedikt, Jensen, Björn, Intxausti, Maider, Blasi, Francesco, Bellinghausen, Carla, Maj, Carlo, Ferrando, Carlos, Horra, Carmen de la, Hanses, Frank, Quereda, Carmen, Mayer, Alena, Skurk, Carsten, Thibeault, Charlotte, Scollo, Chiara, Herr, Christian, Kogevinas, Manolis, Spinner, Christoph D., Malvestiti, Francesco, Gassner, Christoph, Invernizzi, Pietro, Lange, Christoph, Hu, Cinzia, Morilla Romero de la Osa, R., Paccapelo, Cinzia, Lehmann, Clara, Angelini, Claudio, Cappadona, Claudio, Azuure, Clinton, Riveiro-Barciela, Mar, COVICAT study group, Solligård, Erik, Covid-19 Aachen Study (COVAS), Myhre, Ronny, Bianco, Cristiana, Badalamenti, Salvatore, Cea, Cristina, Müller, Fredrik, Hemmrich-Stanisak, Georg, Bellani, Giacomo, Grasselli, Giacomo, Pezzoli, Gianni, Costantino, Giorgio, Vadla, May Sissel, Albano, Giovanni, Niemi, Mari, Buti, María, Cardamone, Giulia, Lippert, Lena J., Bellelli, Giuseppe, Citerio, Giuseppe, Foti, Giuseppe, Lamorte, Giuseppe, Matullo, Giuseppe, Baselli, Guido, Kurihara, Hayato, Neb, Holger, Duga, Stefano, Wacker, Eike M., Gutiérrez-Stampa, María A., Ciesek, Sandra, My, Ilaria, Kurth, Ingo, Hernández, Isabel, Pink, Isabell, Rojas, Itziar de, Galván-Femenia, Iván, Holter, Jan Cato, Bujanda, Luis, Afset, Jan Egil, Heyckendorf, Jan, Kässens, Jan, May, Sandra, Carrabba, Maria, Wienbrandt, Lars, Damås, Jan Kristian, Rybniker, Jan, Altmüller, Janine, Ampuero, Javier, Ceriotti, Ferruccio, Martín, Javier, Erdmann, Jeanette, Banales, Jesús M., Badia, Joan Ramon, Bombace, Sara, Dopazo, Joaquín, Figuera Basso, Maria E., Schneider, Jochen, Blandino Ortiz, Aaron, Bergan, Jonas, Hov, Johannes R., Barretina, Jordi, Walter, Jörn, Hernández Quero, José, Goikoetxea-Aguirre, Josune, Delgado, Juan, Marsal, Sara, Guerrero, Juan M., Fazaal, Julia, Casalone, Elisabetta, Kraft, Julia, Lenz, Tobias L., and Schröder, Julia

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.

Published
2022

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

Author

Federal Ministry of Education and Research (Germany), German Research Foundation, Novo Nordisk Foundation, Ministero della Salute, European Commission, Fondazione Cariplo, Ministero dell'Istruzione, dell'Università e della Ricerca, Generalitat de Catalunya, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Fundación la Caixa, Eusko Jaurlaritza, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Junta de Andalucía, Centro de Investigación Biomédica en Red Epidemiología y Salud Pública (España), Norwegian Research Council, German Center for Lung Research, Airway Research Center North (Germany), Miltenyi Biotec, University of Cologne, Technical University of Munich, Finnish Institute for Molecular Medicine, University of Helsinki, Saarland University, University Hospital Bonn, Bavarian State Ministry of Education, Science and the Arts, Essen University Hospital, Degenhardt, Frauke, Ellinghaus, David, Juzenas, Simonas, Lerga-Jaso, Jon, Wendorff, Mareike, Maya-Miles, Douglas, Uellendahl-Werth, Florian, ElAbd, Hesham, Rühlemann, Malte C., Arora, Jatin, Özer, Onur, Santoro, Luigi, Bacher, Petra, Koehler, Philipp, Tran, Florian, Zoller, Heinz, Binatti, Eleonora, Schulte, Eva C., García Sánchez, Félix, Heidecker, Bettina, Heggelund, Lars, Calderón, Enrique J., Palom, Adriana, Ludwig, Kerstin U., Ramírez, Alfredo, Fernández, Javier, Téllez, Luis, Romero-Gómez, Manuel, Teles, Ana, Scarpini, Elio, Kildal, Anders Benjamin, Biondi, Andrea, Tentorio, Paolo, Asselta, Rosanna, Caballero-Garralda, Andrea, Ganna, Andrea, Gori, Andrea, Glück, Andreas, Lind, Andreas, Peyvandi, Flora, Gallego-Durán, Rocío, Tanck, Anja, Mesonero, Francisco, Castro Blázquez, Pedro, Helbig, Elisa T., Sancho, Cristina, Hinney, Anke, Carreras Nolla, Anna, Fracanzani, Anna Ludovica, Peschuck, Anna, Cavallero, Annalisa, Dyrhol-Riise, Anne Ma, Ruello, Antonella, Julià, Antonio, Rodrigues, Pedro M., Nieto, Rosa, Schaefer, Marco, Ruiz, Agustín, Muscatello, Antonio, Kurth, Florian, Ostadreza, Mahnoosh, Pesenti, Antonio, Voza, Antonio, Rando-Segura, Ariadna, Solier-López, Aurora, España, Pedro Pablo, Schmidt, Axel, Cortes, Beatriz, Mateos, Beatriz, Izquierdo-Sanchez, Laura, Rodríguez-Frías, Francisco, Carpani, Rossana, Nafría-Jiménez, Beatriz, Schaefer, Benedikt, Jensen, Björn, Intxausti, Maider, Cáceres, Mario, Blasi, Francesco, Bellinghausen, Carla, Maj, Carlo, Ferrando, Carlos, Rachele Bettini, Laura, Horra, Carmen de la, Hanses, Frank, Quereda, Carmen, Mayer, Alena, Skurk, Carsten, Hoffmann, Per, Thibeault, Charlotte, Scollo, Chiara, Herr, Christian, Kogevinas, Manolis, Spinner, Christoph D., Sumoy, Lauro, Malvestiti, Francesco, Gassner, Christoph, Invernizzi, Pietro, Lange, Christoph, Holten, Aleksander Rygh, Hu, Cinzia, Morilla Romero de la Osa, R., Paccapelo, Cinzia, Lehmann, Clara, Angelini, Claudio, Cappadona, Claudio, Garrido Chercoles, Adolfo, Azuure, Clinton, Riveiro-Barciela, Mar, COVICAT study group, Rosenstiel, Philip, Solligård, Erik, Covid-19 Aachen Study (COVAS), Myhre, Ronny, Bianco, Cristiana, Badalamenti, Salvatore, Cea, Cristina, Müller, Fredrik, Sander, Leif Erik, Hemmrich-Stanisak, Georg, Bellani, Giacomo, Toapanta, David, Grasselli, Giacomo, Pezzoli, Gianni, Costantino, Giorgio, Vadla, May Sissel, Albano, Giovanni, Niemi, Mari, Buti, María, Cardamone, Giulia, Valsecchi, Maria Grazia, Lippert, Lena J., Salazar, Adolfo de, Bellelli, Giuseppe, Citerio, Giuseppe, Foti, Giuseppe, Lamorte, Giuseppe, Matullo, Giuseppe, Baselli, Guido, Kurihara, Hayato, Neb, Holger, Duga, Stefano, Klein, Sebastian, Contro, Ernesto, Wacker, Eike M., Gutiérrez-Stampa, María A., Ciesek, Sandra, My, Ilaria, Kurth, Ingo, Hernández, Isabel, Pink, Isabell, Rojas, Itziar de, Galván-Femenia, Iván, Holter, Jan Cato, Schommers, Philipp, Hernández-Tejero, María, Bujanda, Luis, Afset, Jan Egil, Heyckendorf, Jan, Kässens, Jan, May, Sandra, Carrabba, Maria, Wienbrandt, Lars, Damås, Jan Kristian, Rybniker, Jan, Suwalski, Phillip, Altmüller, Janine, Vehreschild, Maria J. G. T., Ampuero, Javier, Ceriotti, Ferruccio, Martín, Javier, Erdmann, Jeanette, Banales, Jesús M., Badia, Joan Ramon, Bombace, Sara, Dopazo, Joaquín, Pablo, Raúl de, Figuera Basso, Maria E., Schneider, Jochen, Lihaug Hoff, Dag Arne, Blandino Ortiz, Aaron, Bergan, Jonas, Hov, Johannes R., Barretina, Jordi, Walter, Jörn, Hernández Quero, José, Goikoetxea-Aguirre, Josune, Navas, Enrique, Delgado, Juan, Marsal, Sara, Guerrero, Juan M., Roade, Luisa, Fazaal, Julia, Casalone, Elisabetta, Kraft, Julia, Lenz, Tobias L., Schröder, Julia, Manunta, Maria, Ferrer, Ricard, Acosta-Herrera, Marialbert, D’Angiò, Mariella, Baldini, Marina, Cazzaniga, Marina, Grimsrud, Marit M., Urrechaga, Eloisa, Cornberg, Markus, Pelusi, Serena, Galimberti, Daniela, García-Fernández, Alba-Estela, Volland, Sonja, Bals, Robert, Nöthen, Markus M., Marquié, Marta, Castoldi, Massimo, Cordioli, Mattia, Cecconi, Maurizio, D’Amato, Mauro, Augustin, Max, Tomasi, Melissa, Prati, Daniele, Franke, Andre, Paraboschi, Elvezia Maria, Bandera, Alessandra, Braun, Alice, Boada, Mercè, Dreher, Michael, Blanco-Grau, Albert, Seilmaier, Michael J., Joannidis, Michael, Wittig, Michael, Mazzocco, Michela, Brunak, Søren, Haschka, David, Ciccarelli, Michele, Rodríguez-Gandía, Miguel, Bocciolone, Monica, Cid, Rafael de, Wilfling, Sibylle, Pontali, Emanuele, Miozzo, Monica, Imaz Ayo, Natale, Blay, Natalia, Raychaudhuri, Soumya, Mantovani, Alberto, Berger, Marc M., Chueca, Natalia, Montano, Nicola, Braun, Nicole, Ludwig, Nicole, Valenti, Luca, Marx, Nikolaus, Bosari, Silvano, Martínez, Nilda, Risnes, Kari, Reverter, Enric, Norwegian SARS-CoV-2 Study group, Jiménez, David, Cornely, Oliver A., Witzke, Oliver, Palmieri, Orazio, Zanella, Alberto, Pa COVID-19 Study Group, Karlsen, Tom H., Faverio, Paola, Haider, Sammra, Preatoni, Paoletta, Terranova, Leonardo, Bonfanti, Paolo, Pestaña, David, Omodei, Paolo, Schreiber, Stefan, Heilmann-Heimbach, Stefanie, Aliberti, Stefano, Ripke, Stephan, Dudman, Susanne, Cherubini, Alessandro, Nkambule, Lindokuhle, Wesse, Tanja, Nebel, Almut, Banasik, Karina, Lenning, Ole Bernt, Albillos, Agustín, Zheng, Tenghao, The Humanitas COVID-19 Task Force, The Humanitas Gavazzeni COVID-19 Task Force, Bahmer, Thomas, Eggermann, Thomas, Illig, Thomas, Brenner, Thorsten, Pumarola, Tomàs, Müller, Karl Erik, Knopp, Lisa, Martinelli-Boneschi, Filippo, Medrano, Francisco Javier, Feldt, Torsten, Protti, Alessandro, Arana-Arri, Eunate, Folseraas, Trine, Gonzalez Cejudo, Trinidad, Landmesser, Ulf, Protzer, Ulrike, Gaede, Karoline I., Hehr, Ute, Rimoldi, Valeria, Monzani, Valter, Muñiz-Diaz, Eduardo, Barreira, Ana, Gustad, Lise Tuset, Skogen, Vegard, Keitel, Verena, Kopfnagel, Verena, Aziz, Fátima, Pigazzini, Sara, Aghemo, Alessio, Friaza Patiño, Vicente, Andrade, Victor, Moreno, Victor, Azzolini, Elena, Albrecht, Wolfgang, Lleo, Ana, Peter, Wolfgang, Garbarino, Lucia, Poller, Wolfgang, García-Etxebarria, Koldo, Farré, Xavier, Yi, Xiaoli, Wang, Xiaomin, García, Federico, Khodamoradi, Yascha, 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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 GWAS meta-analysis of a well-characterized cohort of 3,260 COVID-19 patients with respiratory failure and 12,483 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 (HLA) region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a highly pleiotropic ∼0.9-Mb inversion polymorphism 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, 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.

Published
2022

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