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 , Blandino Ortiz Aaron , de Salazar Adolfo , Garrido Chercoles Adolfo , 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 , Carreras Nolla Anna , 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, Aachen Study (COVAS), Bianco Cristiana , Cea Cristina , Sancho Cristina , Hoff Dag Arne Lihaug , 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 , García Sánchez Félix , 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 , Hernández Quero Jose , 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 E K , Gutiérrez-Stampa María A , Carrabba Maria , Figuera Basso Maria E , Valsecchi Maria Grazia , Hernandez-Tejero María , Vehreschild Maria J G T , 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 , Imaz Ayo Natale , 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 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 STORM Study group, The Humanitas Task Force, The Humanitas Gavazzeni Task Force, Bahmer Thomas , Eggermann Thomas , Illig Thomas , Brenner Thorsten , Pumarola Tomas , Feldt Torsten , Folseraas Trine , Gonzalez Cejudo Trinidad , 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 2022

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.