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The ABO blood group locus and a chromosome 3 gene cluster associate with SARS-CoV-2 respiratory failure in an Italian-Spanish genome-wide association analysis

AuthorsEllinghaus, David; Degenhardt, Frauke; Bujanda, Luis; Buti, María; Albillos, Agustín; Invernizzi, Pietro; Fernández, Javier; Prati, Daniele; Baselli, Guido; Asselta, Rosanna; Grimsrud, Marit M.; Wienbrandt, Lars; Uellendahl-Werth, Florian; Zheng, Tenghao; Yi, Xiaoli; Pablo, Raúl de; Garrido Chercoles, Adolfo; Palom, Adriana; Garcia-Fernandez, Alba-Estela; Rodríguez-Frías, Francisco; Zanella, Alberto; Angelini, Claudio; Bandera, Alessandra; Protti, Alessandro; Aghemo, Alessio; Lleo, Ana; Biondi, Andrea; Caballero-Garralda, Andrea; Gori, Andrea ; Tanck, Anja; Latiano, Anna; Fracanzani, Anna Ludovica; Cea, Cristina; Peschuk, Anna; Julià, Antonio; Pesenti, Antonio; Voza, Antonio; Jiménez, David; Mateos, Beatriz; Nafria Jimenez, Beatriz; Quereda, Carmen; Solier, Aurora; Pestaña, David; Sandoval, Elena; Paraboschi, Elvezia Maria; Navas, Enrique; Ceriotti, Ferruccio; Martinelli-Boneschi, Filippo; Peyvandi, Flora; Moreira, Leticia; Blasi, Francesco; Téllez, Luis; Blanco-Grau, Albert; Grasselli, Giacomo; Costantino, Giorgio; Cardamone, Giulia; Foti, Giuseppe; Aneli, Serena; Kurihara, Hayato; ElAbd, Hesham; Santoro, Luigi; My, Ilaria; Martín, Javier; Erdmann, Jeanette; Ferrusquía-Acosta, José; Garcia-Etxebarria, Koldo; Izquierdo-Sanchez, Laura; Bettini, Laura Rachele; Terranova, Leonardo; Scudeller, Luigia; Mesonero, Francisco; Roade, Luisa; Schaefer, Marco; Carrabba, Maria; Riveiro Barciela, Maria del Mar; Figuera Basso, Maria Eloina; Valsecchi, Maria Grazia; Omodei, Paolo; Hernandez-Tejero, María; Acosta-Herrera, Marialbert; D'Angiò, Mariella; Baldini, Marina; Cazzaniga, Marina; Schulzky, Martin; Cecconi, Maurizio; Wittig, Michael; Ciccarelli, Michele; Rodríguez-Gandía, Miguel; Tentorio, Paolo; Bocciolone, Monica; Miozzo, Monica; Braun, Nicole; Martínez, Nilda; Palmieri, Orazio; Faverio, Paola; Preatoni, Paoletta; Bonfanti, Paolo; Castro, Pedro; Rodrigues, Pedro M.; Blandino Ortiz, Aaron; Ferrer Roca, Ricardo; Gualtierotti, Roberta; Nieto, Rosa; Badalamenti, Salvatore; Marsal, Sara; Milani, Chiara; Matullo, Giuseppe; Pelusi, Serena; Monzani, Valter; Wesse, Tanja; Pumarola, Tomas; Rimoldi, Valeria; Bosari, Silvano; Albrecht, Wolfgang; Peter, Wolfgang; Romero Gómez, Manuel; Aziz, Fátima; D'Amato, Mauro; Duga, Stefano; Banales, Jesus M.; Hov, Johannes R.; Folseraas, Trine; Valenti, Luca; Franke, Andre; Karlsen, Tom H.; Kässens, Jan; May, Sandra; Wendorff, Mareike
Issue Date2-Jun-2020
Abstract[Background] Respiratory failure is a key feature of severe Covid-19 and a critical driver of mortality, but for reasons poorly defined affects less than 10% of SARS-CoV-2 infected patients.
[Methods] We included 1,980 patients with Covid-19 respiratory failure at seven centers in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe (Milan, Monza, Madrid, San Sebastian and Barcelona) for a genome-wide association analysis. After quality control and exclusion of population outliers, 835 patients and 1,255 population-derived controls from Italy, and 775 patients and 950 controls from Spain were included in the final analysis. In total we analyzed 8,582,968 single-nucleotide polymorphisms (SNPs) and conducted a metaanalysis of both case-control panels.
[Results] We detected cross-replicating associations with rs11385942 at chromosome 3p21.31 and rs657152 at 9q34, which were genome-wide significant (P<5×10-8) in the meta-analysis of both study panels, odds ratio [OR], 1.77; 95% confidence interval [CI], 1.48 to 2.11; P=1.14×10-10 and OR 1.32 (95% CI, 1.20 to 1.47; P=4.95×10-8), respectively. Among six genes at 3p21.31, SLC6A20 encodes a known interaction partner with angiotensin converting enzyme 2 (ACE2). The association signal at 9q34 was located at the ABO blood group locus and a blood-group-specific analysis showed higher risk for A-positive individuals (OR=1.45, 95% CI, 1.20 to 1.75, P=1.48×10-4) and a protective effect for blood group O (OR=0.65, 95% CI, 0.53 to 0.79, P=1.06×10-5).
[Conclusions] We herein report the first robust genetic susceptibility loci for the development of respiratory failure in Covid-19. Identified variants may help guide targeted exploration of severe Covid19 pathophysiology.
Publisher version (URL)https://doi.org/10.1101/2020.05.31.20114991
Appears in Collections:(IPBLN) Artículos
(VICYT) Colección Especial COVID-19
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