Detailed stratified GWAS analysis for severe COVID-19 in four European populations
Authors: 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 , Lenning Ole Bernt , Myhre Ronny , Vadla May Sissel , Wacker Eike M , Wienbrandt Lars , Ortiz Aaron Blandino , de Salazar Adolfo , Chercoles Adolfo Garrido , Palom Adriana , Ruiz Agustín , Garcia-Fernandez Alba-Estela , Blanco-Grau Albert , Mantovani Alberto , Zanella Alberto , Holten Aleksander Rygh , Mayer Alena , Bandera Alessandra , Cherubini Alessandro , Protti Alessandro , Aghemo Alessio , Gerussi Alessio , Ramirez Alfredo , Braun Alice , Nebel Almut , Barreira Ana , Lleo Ana , Teles Ana , Kildal Anders Benjamin , Biondi Andrea , Caballero-Garralda Andrea , Ganna Andrea , Gori Andrea , Glück Andreas , Lind Andreas , Tanck Anja , Hinney Anke , Nolla Anna Carreras , Fracanzani Anna Ludovica , Peschuck Anna , Cavallero Annalisa , Dyrhol-Riise Anne Ma , Ruello Antonella , Julià Antonio , Muscatello Antonio , Pesenti Antonio , Voza Antonio , Rando-Segura Ariadna , Solier Aurora , Schmidt Axel , Cortes Beatriz , Mateos Beatriz , Nafria-Jimenez Beatriz , Schaefer Benedikt , Jensen Björn , Bellinghausen Carla , Maj Carlo , Ferrando Carlos , de la Horra Carmen , Quereda Carmen , Skurk Carsten , Thibeault Charlotte , Scollo Chiara , Herr Christian , Spinner Christoph D , Gassner Christoph , Lange Christoph , Hu Cinzia , Paccapelo Cinzia , Lehmann Clara , Angelini Claudio , Cappadona Claudio , Azuure Clinton ,   COVICAT study group,   Covid-19 Aachen Study (COVAS), Bianco Cristiana , Cea Cristina , Sancho Cristina , Lihaug Hoff Dag Arne , Galimberti Daniela , Prati Daniele , Haschka David , Jiménez David , Pestaña David , Toapanta David , Muñiz-Diaz Eduardo , Azzolini Elena , Sandoval Elena , Binatti Eleonora , Scarpini Elio , Helbig Elisa T , Casalone Elisabetta , Urrechaga Eloisa , Paraboschi Elvezia Maria , Pontali Emanuele , Reverter Enric , Calderón Enrique J , Navas Enrique , Solligård Erik , Contro Ernesto , Arana-Arri Eunate , Aziz Fátima , Garcia Federico , Sánchez Félix García , Ceriotti Ferruccio , Martinelli-Boneschi Filippo , Peyvandi Flora , Kurth Florian , Blasi Francesco , Malvestiti Francesco , Medrano Francisco J , Mesonero Francisco , Rodriguez-Frias Francisco , Hanses Frank , Müller Fredrik , Hemmrich-Stanisak Georg , Bellani Giacomo , Grasselli Giacomo , Pezzoli Gianni , Costantino Giorgio , Albano Giovanni , Cardamone Giulia , Bellelli Giuseppe , Citerio Giuseppe , Foti Giuseppe , Lamorte Giuseppe , Matullo Giuseppe , Baselli Guido , Kurihara Hayato , Neb Holger , My Ilaria , Kurth Ingo , Hernández Isabel , Pink Isabell , de Rojas Itziar , Galván-Femenia Iván , Holter Jan Cato , Afset Jan Egil , Heyckendorf Jan , Kässens Jan , Damås Jan Kristian , Rybniker Jan , Altmüller Janine , Ampuero Javier , Martín Javier , Erdmann Jeanette , Banales Jesus M , Badia Joan Ramon , Dopazo Joaquin , Schneider Jochen , Bergan Jonas , Barretina Jordi , Walter Jörn , Quero Jose Hernández , Goikoetxea Josune , Delgado Juan , Guerrero Juan M , Fazaal Julia , Kraft Julia , Schröder Julia , Risnes Kari , Banasik Karina , Müller Karl Erik , Gaede Karoline I , Garcia-Etxebarria Koldo , Tonby Kristian , Heggelund Lars , Izquierdo-Sanchez Laura , Bettini Laura Rachele , Sumoy Lauro , Sander Leif Erik , Lippert Lena J , Terranova Leonardo , Nkambule Lindokuhle , Knopp Lisa , Gustad Lise Tuset , Garbarino Lucia , Santoro Luigi , Téllez Luis , Roade Luisa , Ostadreza Mahnoosh , Intxausti Maider , Kogevinas Manolis , Riveiro-Barciela Mar , Berger Marc M , Schaefer Marco , Niemi Mari EK , Gutiérrez-Stampa María A , Carrabba Maria , Figuera Basso Maria E. , Valsecchi Maria Grazia , Hernandez-Tejero María , Vehreschild Maria JGT , Manunta Maria , Acosta-Herrera Marialbert , D’Angiò Mariella , Baldini Marina , Cazzaniga Marina , Grimsrud Marit M , Cornberg Markus , Nöthen Markus M , Marquié Marta , Castoldi Massimo , Cordioli Mattia , Cecconi Maurizio , D’Amato Mauro , Augustin Max , Tomasi Melissa , Boada Mercè , Dreher Michael , Seilmaier Michael J , Joannidis Michael , Wittig Michael , Mazzocco Michela , Ciccarelli Michele , Rodríguez-Gandía Miguel , Bocciolone Monica , Miozzo Monica , Ayo Natale Imaz , Blay Natalia , Chueca Natalia , Montano Nicola , Braun Nicole , Ludwig Nicole , Marx Nikolaus , Martínez Nilda ,   Norwegian SARS-CoV-2 Study group, Cornely Oliver A , Witzke Oliver , Palmieri Orazio ,   Pa COVID-19 Study Group, Faverio Paola , Preatoni Paoletta , Bonfanti Paolo , Omodei Paolo , Tentorio Paolo , Castro Pedro , Rodrigues Pedro M , España Pedro Pablo , Hoffmann Per , Rosenstiel Philip , Schommers Philipp , Suwalski Phillip , de Pablo Raúl , Ferrer Ricard , Bals Robert , Gualtierotti Roberta , Gallego-Durán Rocío , Nieto Rosa , Carpani Rossana , Morilla Rubén , Badalamenti Salvatore , Haider Sammra , Ciesek Sandra , May Sandra , Bombace Sara , Marsal Sara , Pigazzini Sara , Klein Sebastian , Pelusi Serena , Wilfling Sibylle , Bosari Silvano , Volland Sonja , Brunak Søren , Raychaudhuri Soumya , Schreiber Stefan , Heilmann-Heimbach Stefanie , Aliberti Stefano , Ripke Stephan , Dudman Susanne , Wesse Tanja , Zheng Tenghao ,   The Humanitas COVID-19 Task Force,   The Humanitas Gavazzeni COVID-19 Task Force, Bahmer Thomas , Eggermann Thomas , Illig Thomas , Brenner Thorsten , Pumarola Tomas , Feldt Torsten , Folseraas Trine , Cejudo Trinidad Gonzalez , Landmesser Ulf , Protzer Ulrike , Hehr Ute , Rimoldi Valeria , Monzani Valter , Skogen Vegard , Keitel Verena , Kopfnagel Verena , Friaza Vicente , Andrade Victor , Moreno Victor , Albrecht Wolfgang , Peter Wolfgang , Poller Wolfgang , Farre Xavier , Yi Xiaoli , Wang Xiaomin , Khodamoradi Yascha , Karadeniz Zehra , Latiano Anna , Goerg Siegfried , Bacher Petra , Koehler Philipp , Tran Florian , Zoller Heinz , Schulte Eva C , Heidecker Bettina , Ludwig Kerstin U , Fernández Javier , Romero-Gómez Manuel , Albillos Agustín , Invernizzi Pietro , Buti Maria , Duga Stefano , Bujanda Luis , Hov Johannes R , Lenz Tobias L , Asselta Rosanna , de Cid Rafael , Valenti Luca , Karlsen Tom H , Cáceres Mario , Franke Andre 
Published: July 2021

ABSTRACTGiven 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 5threlease of summary statistics from the COVID-19 Host Genetics Initiative, also identified a new locus at 19q13.33, includingNAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.