Title Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality.
Authors Nakanishi, Tomoko , Pigazzini, Sara , Degenhardt, Frauke , Cordioli, Mattia , Butler-Laporte, Guillaume , Maya-Miles, Douglas , Bujanda, Luis , Bouysran, Youssef , Niemi, Mari Ek , Palom, Adriana , Ellinghaus, David , Khan, Atlas , Martínez-Bueno, Manuel , Rolker, Selina , Amitrano, Sara , Roade Tato, Luisa , Fava, Francesca , FinnGen , COVID-19 Host Genetics Initiative (HGI) , Spinner, Christoph D , Prati, Daniele , Bernardo, David , Garcia, Federico , Darcis, Gilles , Fernández-Cadenas, Israel , Holter, Jan Cato , Banales, Jesus M , Frithiof, Robert , Kiryluk, Krzysztof , Duga, Stefano , Asselta, Rosanna , Pereira, Alexandre C , Romero-Gómez, Manuel , Nafría-Jiménez, Beatriz , Hov, Johannes R , Migeotte, Isabelle , Renieri, Alessandra , Planas, Anna M , Ludwig, Kerstin U , Buti, Maria , Rahmouni, Souad , Alarcón-Riquelme, Marta E , Schulte, Eva C , Franke, Andre , Karlsen, Tom H , Valenti, Luca , Zeberg, Hugo , Richards, J Brent , Ganna, Andrea , Rando, Ariadna , Benetti, Elisa , Menon, Amritha , So, Yat S , Goldstein, David B , O'Byrne, Sheila M , Nandakumar, Renu , Lipcsey, Miklos , Hultström, Michael , Bergqvist, Anders , Odeberg-Wernerman, Suzanne , Ampuero, Javier , Gallego-Durán, Rocío , de Salazar, Adolfo , Hernández Quero, Jose , Perez-Tur, Jordi , Protzer, Ulrike , Gonzalez Cejudo, Trinidad , Tamayo, Eduardo , Arana, Eunate , Imaz Ayo, Natale , Rodrigues, Pedro M , Izquierdo, Laura , Dopazo, Joaquín , Aarem, Jeanette , Mathisen, Åse-Berit , Busson, Adeline , Peyrassol, Xavier , Wilkin, Françoise , Pichon, Bruno , Smits, Guillaume , Vandernoot, Isabelle , Tiembe, Nicky , Riveiro-Barciela, Mar , Rodriguez-Frias, Francisco , Guntz, Julien , Vaghi, Massimo , Parzibut, Gilles , Meuris, Christelle , Thys, Marie , Jacques, Jessica , Léonard, Philippe , Frippiat, Frederic , Giot, Jean-Baptiste , Sauvage, Anne-Sophie , von Frenckell, Christian , Lambermont, Bernard , Malaise, Olivier , Bovy, Christophe , Bouquegneau, Antoine , Moutschen, Michel , Misset, Benoit , Guiot, Julien , Marx, Nikolaus , Caldarelli, Gian Piero , Ognibene, Agostino , Pancrazzi, Alessandro , Lorubbio, Maria , Panese, Sandro , Raggi, Pamela , Marciano, Carmen , Perna, Rita , Stella, Alessandra , Biscarini, Filippo , Altmüller, Janine , Capitani, Katia , Lehmann, Clara , Schommers, Philipp , Augustin, Max , Rybniker, Jan , Rygh Holten, Aleksander , Girardis, Massimo , Venturelli, Sophie , Busani, Stefano , Kildal, Anders Benjamin , Garcia-Fernandez, Alba-Estela , Caballero-Garralda, Andrea , Siano, Matteo , Gabrieli, Arianna , Sengupta, Soumitra , Cardamone, Giulia , Cappadona, Claudio , Rimoldi, Valeria , Mantovani, Alberto , Protti, Alessandro , Aghemo, Alessio , Lleo, Ana , Azzolini, Elena , Paraboschi, Elvezia Maria , My, Ilaria , Cecconi, Maurizio , Ionita-Laza, Iuliana , Valente, Serafina , Gravrok, Berit , Ceri, Stefano , Pinoli, Pietro , Afilalo, Marc , Spargi, Genni , Corridi, Marta , Cornberg, Markus , Knopp, Lisa , Keitel, Verena , Jensen, Björn , Feldt, Torsten , D'Arminio Monforte, Antonella , Merlini, Esther , Gaia Miraglia, Federica , Bassetti, Matteo , Castelli, Francesco , Quiros-Roldan, Eugenia , Degli Antoni, Melania , Jenum, Synne , Stiksrud, Birgitte , Hesstvedt, Liv , Pettersen, Frank , Ormaasen, Vidar , Røstad, Kjerstin , Skeie, Linda , Nur, Sarah , Reikvam, Dag Henrik , Egeland Christensen, Erik , Jøntvedt Jørgensen, Marthe , Aballi, Saad , Aarberg Lund, Kristine Marie , Scotton, Pier Giorgio , Andretta, Francesca , Skogen, Vegard , Ferrer, Ricard , Zucchi, Patrizia , Parravicini, Pierpaolo , Øverstad, Siri , Garcia-Etxebarria, Koldo , Picchiotti, Nicola , Cossarizza, Andrea , Karlsson, Philip , Larsson, Anders , Aucella, Filippo , Mazzei, Maria Antonietta , Guerrini, Susanna , Schurr, Erwin , Shang, Ning , Wang, Chen , Gharavi, Ali G , Reilly, Muredach P , Bianchi, Francesco , Perrella, Antonio , Daryl Tylden, Garth , Quist-Paulsen, Else , Kaur Johal, Simreen , Steffensen, Anne , Zanella, Isabella , Russo, Roberta , Andolfo, Immacolata , Iolascon, Achille , Capasso, Mario , Merla, Giuseppe , Parisi, Saverio Giuseppe , Baratti, Stefano , Pendrick, Danielle , Hod, Eldad , Chung, Wendy , Dreher, Michael , Pink, Isabell , Bandini, Maria , Spagnesi, Maurizio , Piacentini, Paolo , Desanctis, Elena , Cappelli, Silvia , Halstensen, Anne Marie , Brynildsen, Jorunn , Bergan, Jonas , Martinelli, Enrico , Nencioni, Cesira , Croci, Leonardo , Tacconi, Danilo , Spertilli, Chiara , Scala, Raffaele , Guidelli, Luca , Gradin, Anna , Galien, Sarah , Rubertsson, Sten , Danielsson, Erik A , Hanslin, Katja , Luther, Tomas , Rosén, Jacob , Bulow, Sara , Von Seth, Magnus , Kawati, Rafael , Ghanima, Waleed , Anedda, Federico , Marcantonio, Simona , Scolletta, Sabino , Franchi, Federico , Feri, Marco , Donati, Alice , Klouman Bekken, Gry , Hermann, Anne , Opsand, Hanne , Martin Woll, Bjørn , Müller, Karl Erik , Bogen, Mette , Austad, Cathrine , Fabbiani, Massimiliano , Rossetti, Barbara , Dyrhol-Riise, Anne Margarita , Tonby, Kristian , Bachetti, Tiziana , Mantovani, Stefania , Umberto Mondelli, Mario , Vecchia, Marco , Bruno, Raffaele , Carella, Massimo , Castori, Marco , Trotta, Tullio , Giannattasio, Ferdinando , Coiro, Gabriella , Ludovisi, Serena , Baselli, Guido , Paccapelo, Cinzia , Ceriotti, Ferruccio , Terranova, Leonardo , Santoro, Luigi , Scudeller, Luigia , Carrabba, Maria , Baldini, Marina , Monzani, Valter , Zanella, Alberto , Bandera, Alessandra , Gori, Andrea , Ludovica Fracanzani, Anna , Pesenti, Antonio , Martinelli-Boneschi, Filippo , Peyvandi, Flora , Grasselli, Giacomo , Costantino, Giorgio , Miozzo, Monica , Montano, Nicola , Gualtierotti, Roberta , Pelusi, Serena , Aliberti, Stefano , Bosari, Silvano , Lamorte, Giuseppe , Ostadreza, Mahnoosh , Carpani, Rossana , Hu, Cinzia , Malvestiti, Francesco , Suardi, Claudia , Müller, Fredrik , D'Amato, Mauro , Tita, Rossella , Mencarelli, Maria Antonietta , Lo Rizzo, Caterina , Pinto, Anna Maria , Illig, Thomas , Volland, Sonja , Popov, Alexander , Dei, Simona , Krieger, Jose E , Jannes, Cinthia E , Ramos Lima, Isabella , Teruo Tada, Mauricio , Velho, Mariliza , Marques, Emanuelle , Valino, Karina , Antinori, Andrea , Vergori, Alessandra , Emiliozzi, Arianna , Rico, Veronica , Aguero, Daiana , Lluis Bedini, Josep , Domingo, Carlos , Robles, Veronica , Soriano, Alex , Sibila, Oriol , Castro, Pedro , Lozano, Francisco , Angelini, Claudio , Kurihara, Hayato , Ciccarelli, Michele , Bocciolone, Monica , Preatoni, Paoletta , Omodei, Paolo , Castoldi, Massimo , CasHumanitas Gavazzeni Covid-Task Forcetoldi, The , Ruiz Jaén, Francisca , Márquez, Leonardo , Rusconi, Stefano , Riva, Agostino , Sanarico, Maurizio , Gabbi, Chiara , Tommasi, Andrea , Paciosi, Francesco , Francisci, Daniela , Schiaroli, Elisabetta , Di Biagio, Antonio , Scaggiante, Renzo , Gatti, Francesca , Mussini, Cristina , Goikoetxea, Josune , Povysil, Gundula , Bhardwaj, Nitin , Winter, Christof , Dudman, Susanne , Lind, Andreas , Maj, Carlo , Kurth, Ingo , Eggermann, Thomas , Nöthen, Markus M , Fazaal, Julia , Schröder, Julia , Blasi, Francesco , Medrano, Francisco J , Dueñas, Carlos , Gutierrez, Sara , Ravaglia, Sabrina , Voza, Antonio , Tentorio, Paolo , Badalamenti, Salvatore , Bombace, Sara , Masetti, Chiara , Colapietro, Francesca , Solano, Simone , Barbieri, Viviana , Humanitas Covid-Task Force, The , Bussotti, Maurizio , La Rovere, Maria Teresa , Sarzi-Braga, Simona , Parati, Gianfranco , Crotti, Lia , Squeo, Gabriella Maria , Forgetta, Vincenzo , Morrison, David R , Ghosh, Biswarup , Laurent, Laetitia , Henry, Danielle , Adra, Darin , Abdullah, Tala , Adeleye, Olumide , Mamlouk, Noor , Kimchi, Nofar , Afrasiabi, Zaman , Rezk, Nardin , Vulesevic, Branka , Bouab, Meriem , Guzman, Charlotte , Petitjean, Louis , Tselios, Chris , Xue, Xiaoqing , Afilalo, Jonathan , Heggelund, Lars , Lena, Fabio , Oliveira, Maureen , Brenner, Bluma , Belisle, Alexandre , Li, Rui , Lepage, Pierre , Ragoussis, Jiannis , Auld, Daniel , Lathrop, G Mark , Mooser, Vincent , Zguro, Kristina , Furini, Simone , Tumbarello, Mario , Montagnani, Francesca , Della Monica, Matteo , Piscopo, Carmelo , Artuso, Rosangela , Perticaroli, Valentina , Doddato, Gabriella , Giliberti, Annarita , Croci, Susanna , Meloni, Ilaria , Beligni, Giada , Fallerini, Chiara , Daga, Sergio , Baldassarri, Margherita , Frullanti, Elisa , Di Sarno, Laura , Palmieri, Maria , Carriero, Miriam Lucia , Alaverdian, Diana , Valentino, Floriana , Bruttini, Mirella , Orduña, Antonio , Eiros, José M , Dominguez-Gil, Marta , Chueca, Natalia , Sanguinetti, Maurizio , Masucci, Luca , Fiz-Lopez, Aida , Arribas, Elisa , de la Cal, Paloma , Wendtner, Clemens-Martin , Intxausti, Maider , Sancho, Cristina , Garrido Chercoles, Adolfo , Gutiérrez-Stampa, María A , España, Pedro P , Urrechaga, Elioisa , Mandalà, Marco , Giorli, Alessia , Salerni, Lorenzo , Conticini, Edoardo , Cantarini, Luca , Frediani, Bruno , Llucia-Carol, Laia , Cullell, Natalia , Raimondi, Francesco , Fevang, Børre , Goffard, Jean-Christophe , Menatti, Elisabetta , Erber, Johanna , Canaccini, Anna , Verzuri, Agnese , Anemoli, Valentina , Coviello, Domenico A , Mancarella, Sandro , Tavecchia, Luisa , Belli, Mary Ann , Rizzi, Marco , Maggiolo, Franco , Ripamonti, Diego , Bargagli, Elena , Bergantini, Laura , D'Alessandro, Miriana , Cameli, Paolo , Bennett, David , Fiorentino, Giuseppe , Georges, Michel , Guerrero, Juan M , DE LA HORRA PADILLA, CARMEN, Calderon, Enrique , Delgado, Juan , Morilla, Rubén , Friaza, Vicente , Gori, Marco , Marsal, Sara , Rojo Rello, Silvia
External publication Si
Means J CLIN INVEST
Scope Article
Nature Científica
JCR Quartile 1
SJR Quartile 1
JCR Impact 19.477
SJR Impact 5.527
Publication date 01/12/2021
DOI 10.1172/JCI152386
Abstract BackgroundThere is considerable variability in COVID-19 outcomes among younger adults, and some of this variation may be due to genetic predisposition.MethodsWe combined individual level data from 13,888 COVID-19 patients (n = 7185 hospitalized) from 17 cohorts in 9 countries to assess the association of the major common COVID-19 genetic risk factor (chromosome 3 locus tagged by rs10490770) with mortality, COVID-19-related complications, and laboratory values. We next performed metaanalyses using FinnGen and the Columbia University COVID-19 Biobank.ResultsWe found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (HR, 1.4; 95% CI, 1.2-1.7). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (OR, 2.1; 95% CI, 1.6-2.6), venous thromboembolism (OR, 1.7; 95% CI, 1.2-2.4), and hepatic injury (OR, 1.5; 95% CI, 1.2-2.0). Risk allele carriers age 60 years and younger had higher odds of death or severe respiratory failure (OR, 2.7; 95% CI, 1.8-3.9) compared with those of more than 60 years (OR, 1.5; 95% CI, 1.2-1.8; interaction, P = 0.038). Among individuals 60 years and younger who died or experienced severe respiratory failure, 32.3% were risk-variant carriers compared with 13.9% of those not experiencing these outcomes. This risk variant improved the prediction of death or severe respiratory failure similarly to, or better than, most established clinical risk factors.ConclusionsThe major common COVID-19 genetic risk factor is associated with increased risks of morbidity and mortality, which are more pronounced among individuals 60 years or younger. The effect was similar in magnitude and more common than most established clinical risk factors, suggesting potential implications for future clinical risk management.
Keywords COVID-19; Genetic variation; Genetics
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