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Detailed stratified GWAS analysis for severe COVID-19 in four European populations
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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.
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DEGENHARDT, Frauke, ELLINGHAUS, David, JUZENAS, Simona, LERGA-JASO, Jon, WENDORFF, Mareike, MAYA-MILES, Douglas, UELLENDAHL-WERTH, Florian, ELABD, Hesham, RÜHLEMANN, Malte c., ARORA, Jatin, ÖZER, Onur, CABALLERO-GARRALDA, Andrea, SOLIER, Aurora, OMODEI, Paolo, BARRETINA, Jordi, PABLO ESPAÑA, Pedro, MARTINELLI-BONESCHI, Filippo, D'AMATO, Mauro, HEYCKENDORF, Jan, KARADENIZ, Zehra, BLAY, Natalia, LANDMESSER, Ulf, ZHENG, Tenghao, PROTZER, Ulrike, TUSET GUSTAD, Lise, BONFANTI, Paolo, MAY, Sandra, PONTALI, Emanuele, GOERG, Siegfried, NAFRIA-JIMENEZ, Beatriz, HEHR, Ute, GUALTIEROTTI, Roberta, MYHRE, Ronny, COSTANTINO, Giorgio, SUWALSKI, Phillip, HANSES, Frank, AUGUSTIN, Max, BRAUN, Alice, ORTIZ, Aaron blandino, CAVALLERO, Annalisa, GASSNER, Christoph, FOLSERAAS, Trine, BELLINGHAUSEN, Carla, SCARPINI, Elio, PARABOSCHI, Elvezia maria, BLASI, Francesco, TANCK, Anja, CONTRO, Ernesto, RYBNIKER, Jan, MÜLLER, Karl erik, CHERUBINI, Antonio, YI, Xiaoli, KURTH, Florian, MANUNTA, Maria, CIESEK, Sandra, PROTTI, Alessandro, BRAUN, Nicole, FIGUERA BASSO, Maria e., MANTOVANI, Alberto, SCHRÖDER, Julia, MARTÍNEZ, Nilda, RODRIGUEZ FRIAS, Francisco, NÖTHEN, Markus m., COVICAT study group, ROJAS, Itziar de, TELES, Ana, GERUSSI, Alesso, ACOSTA-HERRERA, Marialbert, PUMAROLA SUÑÉ, Tomàs, KOGEVINAS, Manolis, SEILMAIER, Michael j., BLANCO-GRAU, Albert, BUJANDA, Luis, WESSE, Tanja, HELBIG, Elisa t., BALDINI, Marina, EGIL AFSET, Jan, WANG, Xiaomin, AGHEMO, Alessio, HERR, Christian, TONBY, Kristian, AMPUERO, Javier, MARSAL, Sara, GARCÍA SÁNCHEZ, Félix, RIPKE, Stephan, SANDOVAL, Elena, SANCHO, Cristina, BELLELLI, Giuseppe, FELDT, Torsten, BETTINI, Laura rachele, JOANNIDIS, Michael, HOLTEN, Aleksander rygh, ALBRECHT, Wolfgang, AZUURE, Clinton, SPINNER, Christoph d., MONZANI, Valter, SCHAEFER, Benedikt, FAZAAL, Julia, BANDERA, Alessandra, MARTÍN, Javier, NIETO, Rosa, HINNEY, Anke, BRENNER, Thorsten, BERGAN, Jonas, ZOLLER, Heinz, CÁCERES, Mario, BOCCIOLONE, Monica, INTXAUSTI, Maider, URRECHAGA, Eloisa, 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TENTORIO, Paolo, BOADA ROVIRA, M., LEHMANN, Clara, ALBILLOS, Agustín, TÉLLEZ, Luis, RAMIREZ, Alfredo, SANDER, Leif erik, BIONDI, Andrea, HOFFMANN, Per, LIND, Andreas, GARCIA-FERNANDEZ, Alba estela, GALIMBERTI, Daniela, LENZ, Tobias l., SCHOMMERS, Philipp, RISNES, Kari, LIHAUG HOFF, Dag arne, FOTI, Giuseppe, STORM STUDY GROUP, The humanitas task force, HEMMRICH-STANISAK, Georg, BALS, Robert, POLLER, Wolfgang, BINATTI, Eleonora, MUSCATELLO, Antonio, MEDRANO, Francisco j., BOSARI, Silvano, LATIANO, Anna, CORNBERG, Markus, ASSELTA, Rosanna, DREHER, Michael, MORENO AGUADO, Víctor, R HOV, Johannes, ANGELINI, Claudio, AZIZ, Fátima, IZQUIERDO-SANCHEZ, Laura, FRANKE, Andre, GARCIA, Federico, MATULLO, Giuseppe, CAZZANIGA, Marina, HERNÁNDEZ, Isabel, PINK, Isabell, DE SALAZAR, Adolfo, SKOGEN, Vegard, RIMOLDI, Valeria, CARRERAS NOLLA, Anna, MONTANO, Nicola, CORDIOLI, Mattia, HEIDECKER, Bettina, MA DYRHOL-RIISE, Anne, PIGAZZINI, Sara, KÄSSENS, Jan, BADIA, Joan ramon, NEBEL, Almut, GAEDE, Karoline i., LIPPERT, Lena j., GLÜCK, Andreas, HASCHKA, David, SCHAEFER, Marco, GARBARINO, Lucia, CASALONE, Elisabetta, DELGADO, Juan, SCHMIDT, Axel, SKURK, Carsten, ROADE, Luisa, FARRE, Xavier, OSTADREZA, Mahnoosh, BERGER, Marc m., LANGE, Christoph, LENNING, Ole bernt, MORILLA, Rubén, QUEREDA, Carmen, MARQUIÉ, Marta, MATEOS, Beatriz, LUDWIG, Kerstin u., HU, Cinzia, KOEHLER, Philipp, IMAZ AYO, Natale, VOLLAND, Sonja, KRAFT, Julia, ROMERO-GÓMEZ, Manuel, PRATI, Danielle, BIANCO, Cristiana, ALBANO, Giovanni, RANDO SEGURA, Ariadna, PACCAPELO, Cinzia, MALVESTITI, Francesco, VALENTI, Luca, MARX, Nikolaus, CAPPADONA, Claudio, BASELLI, Guido, ZANELLA, Alberto, MIOZZO, Monica, DUDMAN, Susanne, TERRANOVA, Leonardo, JULIÀ CANO, Antonio, CASTRO REBOLLO, Pedro, FAVERIO, Paola, MAYER, Alena, BARREIRA, Ana, CHUECA, Natalia, GARCIA-ETXEBARRIA, Koldo, KURTH, Ingo, SCHNEIDER, Jochen, GUTIÉRREZ-STAMPA, María a., JENSEN, Björn, INVERNIZZI, Pietro, FERNÁNDEZ CALLES, Javier, D'ANGIÒ, Mariella, PABLO, Raúl de, GALLEGO-DURÁN, Rocío, MARTINELLI-BONESCHI, Filippo, SANTORO, Luigi, HAIDER, Sammra, FRACANZANI, Anna ludovica, MUÑIZ-DIAZ, Eduard, LUDWIG, Nicole, KEITEL, Verena, KURIHARA, Hayato, PRESENTI, Antonio, CITERIO, Giuseppe, HORRA, C. de la, Norwegian SARS-CoV-2 Study group, FRIAZA, Vicente, DUGA, Stefano, ERDMANN, Jeanette, PALMIERI, Orazio, PESTAÑA, David, SCHULTE, Eva c., RUIZ, Agustín, WIENBRANDT, Lars, VADLA, May sissel, VEHRESCHILD, Maria j.g.t., GRIMSRUD, Marit m., MAJ, Carlo, ANDRADE, Victor, WITZKE, Oliver, VOZA, Antonio, PESCHUCK, Anna, Aachen Study (COVAS), WACKER, Eike m., RAYCHAUDHURI, Soumya, FERRER, Ricard, TOAPANTA, David, CEA, Cristina, CICCARELLI, Michele, RODRÍGUEZ-GANDÍA, Miguel, SCHREIBER, Stefan, DOPAZO, Joaquín, DAMÅS, Jan kristian, PEYVANDI, Flora, ALTMÜLLER, Janine, CALDERÓN, Enrique j., HELBIG, Elisa t., WITTING, Michael, GANNA, Andrea, LAMORTE, Giuseppe, CATO HOLTER, Jan, CORNELY, Oliver a., THIBEAULT, Charlotte, ROSENSTIEL, Philip, NIEMI, Mari e. k., TRAN, Florian, PELUSI, Serena, SOLLIGÅRD, Erik, CARPANI, Rossana, MAZZOCCO, Michela, KARLSEN, Tom h., BELLANI, Giacomo, NEB, Holger, BANASIK, Karina, KHODAMORADI, Yascha, WILFLING, Sibylle, HERNÁNDEZ QUERO, José. Detailed stratified GWAS analysis for severe COVID-19 in four European populations. _Human Molecular Genetics_. 2022. Vol. 31, núm. 23, pàgs. 3945-3966. [consulta: 22 de gener de 2026]. ISSN: 0964-6906. [Disponible a: https://hdl.handle.net/2445/198771]