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Hum Mol Genet
. 2022 Jul 15;ddac158.
doi: 10.1093/hmg/ddac158. Online ahead of print.
Detailed stratified GWAS analysis for severe COVID-19 in four European populations
Frauke Degenhardt 1 , David Ellinghaus 1 2 , Simonas Juzenas 1 3 , Jon Lerga-Jaso 4 , Mareike Wendorff 1 , Douglas Maya-Miles 5 6 7 , Florian Uellendahl-Werth 1 , Hesham ElAbd 1 , Malte C Rühlemann 1 8 , Jatin Arora 9 10 11 12 13 , Onur Özer 14 15 , Ole Bernt Lenning 16 17 , Ronny Myhre 18 , May Sissel Vadla 17 19 , Eike M Wacker 1 , Lars Wienbrandt 1 , Aaron Blandino Ortiz 20 , Adolfo Salazar 21 22 , Adolfo Garrido Chercoles 23 , Adriana Palom 24 25 , Agustín Ruiz 26 27 , Alba-Estela Garcia-Fernandez 28 , Albert Blanco-Grau 28 , Alberto Mantovani 29 30 , Alberto Zanella 31 32 , Aleksander Rygh Holten 33 34 , Alena Mayer 35 , Alessandra Bandera 31 32 , Alessandro Cherubini 32 , Alessandro Protti 29 30 , Alessio Aghemo 29 30 , Alessio Gerussi 36 37 , Alfredo Ramirez 38 39 40 41 42 , Alice Braun 35 , Almut Nebel 1 , Ana Barreira 25 , Ana Lleo 29 30 , Ana Teles 14 15 , Anders Benjamin Kildal 43 , Andrea Biondi 44 , Andrea Caballero-Garralda 45 , Andrea Ganna 46 , Andrea Gori 32 47 , Andreas Glück 48 , Andreas Lind 49 , Anja Tanck 1 , Anke Hinney 50 , Anna Carreras Nolla 51 , Anna Ludovica Fracanzani 31 32 , Anna Peschuck 1 , Annalisa Cavallero 52 , Anne Ma Dyrhol-Riise 34 53 , Antonella Ruello 54 , Antonio Julià 24 , Antonio Muscatello 32 , Antonio Pesenti 31 32 , Antonio Voza 29 30 , Ariadna Rando-Segura 55 56 , Aurora Solier 57 , Axel Schmidt 58 , Beatriz Cortes 51 , Beatriz Mateos 6 59 , Beatriz Nafria-Jimenez 23 , Benedikt Schaefer 60 61 , Björn Jensen 62 , Carla Bellinghausen 63 , Carlo Maj 64 , Carlos Ferrando 65 66 , Carmen Horra 5 7 67 68 69 , Carmen Quereda 70 , Carsten Skurk 35 , Charlotte Thibeault 35 , Chiara Scollo 71 , Christian Herr 72 , Christoph D Spinner 73 , Christoph Gassner 1 74 , Christoph Lange 75 76 77 , Cinzia Hu 78 , Cinzia Paccapelo 32 , Clara Lehmann 79 80 81 , Claudio Angelini 82 , Claudio Cappadona 30 , Clinton Azuure 14 15 , COVICAT study group, Aachen Study (COVAS); Cristiana Bianco 32 , Cristina Cea 28 , Cristina Sancho 83 , Dag Arne Lihaug Hoff 84 85 , Daniela Galimberti 31 32 , Daniele Prati 32 , David Haschka 86 , David Jiménez 57 , David Pestaña 87 , David Toapanta 66 , Eduardo Muñiz-Diaz 88 , Elena Azzolini 29 30 , Elena Sandoval 66 , Eleonora Binatti 36 37 , Elio Scarpini 31 32 , Elisa T Helbig 35 , Elisabetta Casalone 89 , Eloisa Urrechaga 90 91 , Elvezia Maria Paraboschi 29 30 , Emanuele Pontali 92 , Enric Reverter 66 , Enrique J Calderón 5 7 67 68 69 , Enrique Navas 70 , Erik Solligård 93 94 , Ernesto Contro 95 , Eunate Arana-Arri 96 , Fátima Aziz 66 , Federico Garcia 21 22 97 , Félix García Sánchez 98 , Ferruccio Ceriotti 32 , Filippo Martinelli-Boneschi 99 100 , Flora Peyvandi 101 102 , Florian Kurth 35 103 , Francesco Blasi 104 105 , Francesco Malvestiti 31 , Francisco J Medrano 7 67 68 69 106 , Francisco Mesonero 6 59 , Francisco Rodriguez-Frias 6 24 56 107 , Frank Hanses 108 109 , Fredrik Müller 34 49 , Georg Hemmrich-Stanisak 1 , Giacomo Bellani 110 111 , Giacomo Grasselli 31 32 , Gianni Pezzoli 112 , Giorgio Costantino 31 32 , Giovanni Albano 54 , Giulia Cardamone 30 , Giuseppe Bellelli 111 113 , Giuseppe Citerio 111 114 , Giuseppe Foti 110 111 , Giuseppe Lamorte 32 , Giuseppe Matullo 89 , Guido Baselli 32 , Hayato Kurihara 82 , Holger Neb 115 , Ilaria My 29 , Ingo Kurth 116 , Isabel Hernández 26 27 , Isabell Pink 117 , Itziar Rojas 26 27 , Iván Galván-Femenia 51 , Jan Cato Holter 34 49 , Jan Egil Afset 84 118 , Jan Heyckendorf 75 76 77 , Jan Kässens 1 , Jan Kristian Damås 119 120 , Jan Rybniker 79 80 121 , Janine Altmüller 122 , Javier Ampuero 5 6 7 67 123 , Javier Martín 124 , Jeanette Erdmann 125 126 127 , Jesus M Banales 6 128 129 , Joan Ramon Badia 130 , Joaquin Dopazo 7 131 , Jochen Schneider 73 , Jonas Bergan 132 , Jordi Barretina 133 , Jörn Walter 134 , Jose Hernández Quero 21 135 , Josune Goikoetxea 136 , Juan Delgado 5 7 67 68 69 , Juan M Guerrero 5 7 67 , Julia Fazaal 58 , Julia Kraft 35 , Julia Schröder 58 , Kari Risnes 120 137 , Karina Banasik 2 , Karl Erik Müller 138 , Karoline I Gaede 139 140 141 , Koldo Garcia-Etxebarria 6 128 , Kristian Tonby 34 53 , Lars Heggelund 138 142 , Laura Izquierdo-Sanchez 6 128 143 , Laura Rachele Bettini 44 , Lauro Sumoy 133 , Leif Erik Sander 35 , Lena J Lippert 35 , Leonardo Terranova 32 , Lindokuhle Nkambule 144 145 , Lisa Knopp 62 , Lise Tuset Gustad 93 146 , Lucia Garbarino 147 , Luigi Santoro 32 , Luis Téllez 6 59 , Luisa Roade 6 25 56 , Mahnoosh Ostadreza 32 , Maider Intxausti 83 , Manolis Kogevinas 68 148 149 150 , Mar Riveiro-Barciela 6 25 56 , Marc M Berger 151 , Marco Schaefer 152 , Mari E K Niemi 46 , María A Gutiérrez-Stampa 153 , Maria Carrabba 78 , Maria E Figuera Basso 1 , Maria Grazia Valsecchi 154 , María Hernandez-Tejero 66 , Maria J G T Vehreschild 155 , Maria Manunta 32 , Marialbert Acosta-Herrera 124 , Mariella D'Angiò 44 , Marina Baldini 32 , Marina Cazzaniga 156 , Marit M Grimsrud 34 157 158 , Markus Cornberg 159 , Markus M Nöthen 58 , Marta Marquié 26 27 , Massimo Castoldi 54 , Mattia Cordioli 46 , Maurizio Cecconi 29 30 , Mauro D'Amato 129 160 161 , Max Augustin 79 80 81 , Melissa Tomasi 32 , Mercè Boada 26 27 , Michael Dreher 162 , Michael J Seilmaier 163 , Michael Joannidis 164 , Michael Wittig 1 , Michela Mazzocco 147 , Michele Ciccarelli 82 , Miguel Rodríguez-Gandía 6 59 , Monica Bocciolone 82 , Monica Miozzo 31 78 , Natale Imaz Ayo 96 , Natalia Blay 51 , Natalia Chueca 22 , Nicola Montano 31 32 , Nicole Braun 1 165 , Nicole Ludwig 166 , Nikolaus Marx 167 , Nilda Martínez 168 , Norwegian SARS-CoV-2 Study group; Oliver A Cornely 40 79 81 169 , Oliver Witzke 170 , Orazio Palmieri 171 , Pa Study Group; Paola Faverio 111 172 , Paoletta Preatoni 82 , Paolo Bonfanti 111 173 , Paolo Omodei 82 , Paolo Tentorio 29 , Pedro Castro 66 , Pedro M Rodrigues 6 128 129 143 , Pedro Pablo España 90 , Per Hoffmann 58 , Philip Rosenstiel 1 , Philipp Schommers 79 80 81 , Phillip Suwalski 35 , Raúl Pablo 20 , Ricard Ferrer 174 , Robert Bals 72 , Roberta Gualtierotti 31 32 , Rocío Gallego-Durán 5 6 7 , Rosa Nieto 57 , Rossana Carpani 32 , Rubén Morilla 5 7 67 68 69 , Salvatore Badalamenti 29 , Sammra Haider 175 , Sandra Ciesek 176 177 , Sandra May 1 , Sara Bombace 29 30 , Sara Marsal 24 , Sara Pigazzini 46 , Sebastian Klein 164 , Serena Pelusi 31 32 , Sibylle Wilfling 109 178 179 , Silvano Bosari 31 32 , Sonja Volland 180 , Søren Brunak 2 , Soumya Raychaudhuri 9 10 11 12 13 181 , Stefan Schreiber 1 48 , Stefanie Heilmann-Heimbach 58 , Stefano Aliberti 29 30 , Stephan Ripke 35 , Susanne Dudman 34 49 , Tanja Wesse 1 , Tenghao Zheng 182 , STORM Study group, The Humanitas Task Force, The Humanitas Gavazzeni Task Force; Thomas Bahmer 48 , Thomas Eggermann 116 , Thomas Illig 180 , Thorsten Brenner 151 , Tomas Pumarola 183 184 , Torsten Feldt 62 , Trine Folseraas 34 157 158 185 , Trinidad Gonzalez Cejudo 186 , Ulf Landmesser 187 , Ulrike Protzer 188 189 , Ute Hehr 178 , Valeria Rimoldi 30 , Valter Monzani 32 , Vegard Skogen 190 191 , Verena Keitel 62 , Verena Kopfnagel 180 , Vicente Friaza 5 7 67 68 69 , Victor Andrade 38 39 , Victor Moreno 68 192 193 194 , Wolfgang Albrecht 1 , Wolfgang Peter 152 195 , Wolfgang Poller 35 , Xavier Farre 51 , Xiaoli Yi 1 , Xiaomin Wang 35 , Yascha Khodamoradi 155 , Zehra Karadeniz 35 , Anna Latiano 171 , Siegfried Goerg 196 , Petra Bacher 1 197 , Philipp Koehler 40 79 80 , Florian Tran 1 48 , Heinz Zoller 60 61 , Eva C Schulte 188 198 199 , Bettina Heidecker 35 , Kerstin U Ludwig 58 , Javier Fernández 66 200 , Manuel Romero-Gómez 5 6 7 67 123 , Agustín Albillos 6 59 , Pietro Invernizzi 36 37 , Maria Buti 6 25 56 , Stefano Duga 29 30 , Luis Bujanda 6 128 , Johannes R Hov 34 157 158 185 , Tobias L Lenz 14 15 , Rosanna Asselta 29 30 , Rafael Cid 51 , Luca Valenti 31 32 , Tom H Karlsen 34 157 158 185 , Mario Cáceres 4 201 , Andre Franke 1 202
Affiliations
- PMID: 35848942
- DOI: 10.1093/hmg/ddac158
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 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 (HLA) 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.