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

著者: Frauke Degenhardt, David Ellinghaus, Simonas Juzėnas, Jon Lerga-Jaso, Mareike Wendorff, Douglas Maya‐Miles, Florian Uellendahl-Werth, Hesham ElAbd, Malte Rühlemann, Jatin Arora, Onur Özer, Ole Bernt Lenning, Ronny Myhre, May Sissel Vadla, Eike Matthias Wacker, Lars Wienbrandt, Aaron Blandino Ortíz, Adolfo de Salazar, Adolfo Garrido Chercoles, Adriana Palom, Agustı́n Ruiz, Alba-Estela Garcia-Fernandez, Albert Blanco‐Grau, Alberto Mantovani, Alberto Zanella, Aleksander Rygh Holten, Alena Mayer, Alessandra Bandera, Alessandro Cherubini, Alessandro Protti, Alessio Aghemo, Alessio Gerussi, Alfredo Ramı́rez, Alice Braun, Almut Nebel, Ana Barreira, Ana Lleò, Ana Teles, Anders Benjamin Kildal, Andrea Biondi, Andrea Caballero-Garralda, Andrea Ganna, Andrea Gori, Andreas Glück, Andreas Lind, Anja Tanck, Anke Hinney, Anna Carreras, Anna Ludovica Fracanzani, Anna Peschuck, Annalisa Cavallero, Anne Ma Dyrhol‐Riise, Antonella Ruello, Antonio Julià, Antonio Muscatello, Antonio Artigas, Antonio Voza, Ariadna Rando‐Segura, Aurora Solier, Axel Schmidt, Beatriz Cortés, Beatriz Muñoz, Beatriz Nafría-Jiménez, Benedikt Schaefer, Björn‐Erik Ole Jensen, Carla Bellinghausen, Carlo Maj, Carlos Ferrando, Carmen de la Horra, Carmen Quereda, Carsten Skurk, Charlotte Thibeault, Chiara Scollo, Christian Herr, Christoph D. Spinner, Christoph Gassner, Christoph Lange, Cinzia Hu, Cinzia Paccapelo, Clara Lehmann, Claudio Angelini, Claudio Cappadona, Clinton Azuure, COVICAT study group, Aachen Study (COVAS), Cristiana Bianco, Cristina Cea, Cristina Sancho, Dag Arne Lihaug Hoff, Daniela Galimberti, Daniele Prati, David Haschka, David Jiménez, David Pestaña, David Toapanta, Eduardo Muñiz‐Díaz, Elena Azzolini, Elena Sandoval, Eleonora Binatti, Elio Scarpini, Elisa T. Helbig, Elisabetta Casalone, Eloísa Urrechaga, Elvezia Maria Paraboschi, Emanuele Pontali, Enric Reverter, Enrique J. Calderón, Enrique Navas, Erik Solligård, Ernesto Contro, Eunate Arana‐Arri, Fátima Aziz, Féderico García, Félix García Sánchez, Ferruccio Ceriotti, Filippo Martinelli Boneschi, Flora Peyvandi, Florian Kurth, Francesco Blasi, Francesco Malvestiti, Francisco J. Medrano, Francisco Mesonero, Francisco Rodríguez‐Frias, Frank Hanses, Fredrik Müller, Georg Hemmrich‐Stanisak, Giacomo Bellani, Giacomo Grasselli, Gianni Pezzoli, Giorgio Costantino, Giovanni Albano, Giulia Cardamone, Giuseppe Bellelli, Giuseppe Citerio, Giuseppe Foti, Giuseppe Lamorte, Giuseppe Matullo, Guido Baselli, Hayato Kurihara, Holger Neb, Ilaria My, Ingo Kurth, Isabel Hernández, Isabell Pink, Itziar de Rojas, Iván Galván‐Femenía, Jan Cato Holter, Jan Egil Afset, Jan Heyckendorf, Jan Christian Kässens, Jan Kristian Damås, Jan Rybniker, Janine Altmüller, Javier Ampuero, Javier Martı́n, Jeanette Erdmann, Jesús M. Bañales, Joan R. Badia, Joaquı́n Dopazo, Jochen Schneider, Jonas Bergan, Jordi Barretina, Jörn Walter, José Hernández‐Quero, Josune Goikoetxea, Juan Delgado, Juan M. Guerrero, Julia Fazaal, Julia Kraft, Julia Schröder, Kari Risnes, Karina Banasik, Karl Erik Müller, Karoline I. Gaede, Koldo García‐Etxebarria, Kristian Tonby, Lars Heggelund, Laura Izquierdo‐Sánchez, Laura Rachele Bettini, Lauro Sumoy, Leif Erik Sander, Lena J. Lippert, Leonardo Terranova, Lindokuhle Nkambule, Lisa Knopp, Lise Tuset Gustad, Lucia Garbarino, Luigi Santoro, Luís Téllez, Luisa Roade, Mahnoosh Ostadreza, Maider Intxausti, Manolis Kogevinas, Mar Riveiro‐Barciela, Marc Moritz Berger, Marco Schaefer, Mari Niemi, María A. Gutiérrez-Stampa, Maria Carrabba, Maria E. Figuera Basso, Maria Grazia Valsecchi, María Hernandez-Tejero, Maria J. G. T. Vehreschild, Maria Manunta, Marialbert Acosta‐Herrera, Mariella D’Angiò, Marina Baldini, Marina Elena Cazzaniga, Marit M. Grimsrud, Markus Cornberg, Markus M. Nöthen, Marta Marquié, Massimo Castoldi, Mattia Cordioli, Maurizio Cecconi, Mauro D’Amato, Max Augustin, Melissa Tomasi, Merçé Boada, Michael Dreher, Michael Seilmaier, Michael Joannidis, Michael Wittig, Michela Mazzocco, Michele Ciccarelli, Miguel Ángel Rodríguez-Gandía, Monica Bocciolone, Monica Miozzo, Natale Imaz Ayo, Natàlia Blay, Natalia Chueca, Nicola Montano, Nicole Braun, Nicole Ludwig, Nikolaus Marx, Nilda Martínez, Norwegian SARS-CoV-2 Study group, Oliver A. Cornely, Oliver Witzke, Orazio Palmieri, Pa Study Group, Paola Faverio, Paoletta Preatoni, Paolo Bonfanti, Paolo Omodei, Paolo Tentorio, Pedro Castro, Pedro M. Rodrigues, Pedro Pablo España, Per Hoffmann, Philip Rosenstiel, Philipp Schommers, Phillip Suwalski, Raúl de Pablo, Ricard Ferrer, Robert Bals, Roberta Gualtierotti, Rocío Gallego‐Durán, Rosa Nieto, Rossana Carpani, Rubén Morilla, Salvatore Badalamenti, Sammra Haider, Sandra Ciesek, Sandra May, Sara Bombace, Sara Marsal, Sara Pigazzini, Sebastian Klein, Serena Pelusi, Sibylle Wilfling, Silvano Bòsari, Sonja Volland, Søren Brunak, Soumya Raychaudhuri, Stefan Schreiber, Stefanie Heilmann‐Heimbach, Stefano Aliberti, Stephan Ripke, Susanne Dudman, Tanja Wesse, Tenghao Zheng, The STORM Study group, The Humanitas Task Force, The Humanitas Gavazzeni Task Force, Thomas Bahmer, Thomas Eggermann, Thomas Illig, Thorsten Brenner, Tomàs Pumarola, Torsten Feldt, Trine Folseraas, Trinidad González Cejudo, Ulf Landmesser, Ulrike Protzer, Ute Hehr, Valeria Rimoldi, Valter Monzani, Vegard Skogen, Verena Keitel, Verena Kopfnagel, Vicente Friaza, Víctor Andrade, Vı́ctor Moreno, Wolfgang Albrecht, Wolfgang Peter, Wolfgang Poller, Xavier Farré, Xiaoli Yi, Xiaomin Wang, Yascha Khodamoradi, Zehra Karadeniz, Anna Latiano, Siegfried Goerg, Petra Bächer, Philipp Koehler, Florian Tran, Heinz Zoller, Eva C. Schulte, Bettina Heidecker, Kerstin U. Ludwig, Javier Fernández, Manuel Romero‐Gómez, Agustı́n Albillos, Pietro Invernizzi, Marı́a Buti, Stefano Duga, Luís Bujanda, Johannes R. Hov, Tobias L. Lenz, Rosanna Asselta, Rafael de Cid, Luca Valenti, Tom H. Karlsen, Mario Cáceres, André Franke - Human Molecular Genetics 2022 被引用: 101

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.