Detailed stratified GWAS analysis for severe COVID-19 in four European populations.
Human molecular genetics
Authors:
Frauke Degenhardt, David Ellinghaus, Simonas Juzenas, Jon Lerga-Jaso, Mareike Wendorff, Douglas Maya-Miles, Florian Uellendahl-Werth, Hesham ElAbd, Malte C Rühlemann, Jatin Arora, Onur Özer, Ole Bernt Lenning, Ronny Myhre, May Sissel Vadla, Eike M Wacker, Lars Wienbrandt, Aaron Blandino Ortiz, Adolfo de Salazar, Adolfo Garrido Chercoles, Adriana Palom, Agustín 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 Ramirez, Alice Braun, Almut Nebel, Ana Barreira, Ana Lleo, Ana Teles, Anders Benjamin Kildal, Andrea Biondi, Andrea Caballero-Garralda, Andrea Ganna, Andrea Gori, Andreas Glück, Andreas Lind, Anja Tanck, Anke Hinney, Anna Carreras Nolla, Anna Ludovica Fracanzani, Anna Peschuck, Annalisa Cavallero, Anne Ma Dyrhol-Riise, Antonella Ruello, Antonio Julià, Antonio Muscatello, Antonio Pesenti, Antonio Voza, Ariadna Rando-Segura, Aurora Solier, Axel Schmidt, Beatriz Cortes, Beatriz Mateos, Beatriz Nafria-Jimenez, Benedikt Schaefer, Björn 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, Cristiana Bianco, Cristina Cea, Cristina Sancho, Dag Arne Lihaug Hoff, Daniela Galimberti, Daniele Prati, David Haschka, David Jiménez, David Pestaña, David Toapanta, Eduardo Muñiz-Diaz, Elena Azzolini, Elena Sandoval, Eleonora Binatti, Elio Scarpini, Elisa T Helbig, Elisabetta Casalone, Eloisa Urrechaga, Elvezia Maria Paraboschi, Emanuele Pontali, Enric Reverter, Enrique J Calderón, Enrique Navas, Erik Solligård, Ernesto Contro, Eunate Arana-Arri, Fátima Aziz, Federico Garcia, Félix García Sánchez, Ferruccio Ceriotti, Filippo Martinelli-Boneschi, Flora Peyvandi, Florian Kurth, Francesco Blasi, Francesco Malvestiti, Francisco J Medrano, Francisco Mesonero, Francisco Rodriguez-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-Femenia, Jan Cato Holter, Jan Egil Afset, Jan Heyckendorf, Jan Kässens, Jan Kristian Damås, Jan Rybniker, Janine Altmüller, Javier Ampuero, Javier Martín, Jeanette Erdmann, Jesus M Banales, Joan Ramon Badia, Joaquin Dopazo, Jochen Schneider, Jonas Bergan, Jordi Barretina, Jörn Walter, Jose 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 Garcia-Etxebarria, Kristian Tonby, Lars Heggelund, Laura Izquierdo-Sanchez, Laura Rachele Bettini, Lauro Sumoy, Leif Erik Sander, Lena J Lippert, Leonardo Terranova, Lindokuhle Nkambule, Lisa Knopp, Lise Tuset Gustad, Lucia Garbarino, Luigi Santoro, Luis Téllez, Luisa Roade, Mahnoosh Ostadreza, Maider Intxausti, Manolis Kogevinas, Mar Riveiro-Barciela, Marc M Berger, Marco Schaefer, Mari E K 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 Cazzaniga, Marit M Grimsrud, Markus Cornberg, Markus M Nöthen, Marta Marquié, Massimo Castoldi, Mattia Cordioli, Maurizio Cecconi, Mauro D'Amato, Max Augustin, Melissa Tomasi, Mercè Boada, Michael Dreher, Michael J Seilmaier, Michael Joannidis, Michael Wittig, Michela Mazzocco, Michele Ciccarelli, Miguel Rodríguez-Gandía, Monica Bocciolone, Monica Miozzo, Natale Imaz Ayo, Natalia Blay, Natalia Chueca, Nicola Montano, Nicole Braun, Nicole Ludwig, Nikolaus Marx, Nilda Martínez, Oliver A Cornely, Oliver Witzke, Orazio Palmieri, 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 Bosari, Sonja Volland, Søren Brunak, Soumya Raychaudhuri, Stefan Schreiber, Stefanie Heilmann-Heimbach, Stefano Aliberti, Stephan Ripke, Susanne Dudman, Tanja Wesse, Tenghao Zheng, Thomas Bahmer, Thomas Eggermann, Thomas Illig, Thorsten Brenner, Tomas Pumarola, Torsten Feldt, Trine Folseraas, Trinidad Gonzalez Cejudo, Ulf Landmesser, Ulrike Protzer, Ute Hehr, Valeria Rimoldi, Valter Monzani, Vegard Skogen, Verena Keitel, Verena Kopfnagel, Vicente Friaza, Victor Andrade, Victor Moreno, Wolfgang Albrecht, Wolfgang Peter, Wolfgang Poller, Xavier Farre, Xiaoli Yi, Xiaomin Wang, Yascha Khodamoradi, Zehra Karadeniz, Anna Latiano, Siegfried Goerg, Petra Bacher, Philipp Koehler, Florian Tran, Heinz Zoller, Eva C Schulte, Bettina Heidecker, Kerstin U Ludwig, Javier Fernández, Manuel Romero-Gómez, Agustín Albillos, Pietro Invernizzi, Maria Buti, Stefano Duga, Luis Bujanda, Johannes R Hov, Tobias L Lenz, Rosanna Asselta, Rafael de Cid, Luca Valenti, Tom H Karlsen, Mario Cáceres, Andre Franke
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.