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SARS-CoV-2 proteins

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

    Authors: David Ellinghaus; Frauke Degenhardt; Luis Bujanda; Maria Buti; Agustin Albillos; Pietro Invernizzi; Javier Fernandez; Daniele Prati; Guido Baselli; Rosanna Asselta; Marit Maehle Grimsrud; Chiara Milani; Fatima Aziz; Jan Kassens; Sandra May; Mareike Wendorff; Lars Wienbrandt; Florian Uellendahl-Werth; Tenghao Zheng; Xiaoli Yi; Raul de Pablo; Adolfo Garrido Chercoles; Adriana Palom; Alba-Estela Garcia-Fernandez; Francisco Rodriguez-Frias; Alberto Zanella; Alessandra Bandera; Alessandro Protti; Alessio Aghemo; Ana Lleo de Nalda; Andrea Biondi; Andrea Caballero-Garralda; Andrea Gori; Anja Tanck; Anna Latiano; Anna Ludovica Fracanzani; Anna Peschuck; Antonio Julia; Antonio Pesenti; Antonio Voza; David Jimenez; Beatriz Mateos; Beatriz Nafria Jimenez; Carmen Quereda; Claudio Angelini; Cristina Cea; Aurora Solier; David Pestana; Elena Sandoval; Elvezia Maria Paraboschi; Enrique Navas; Ferruccio Ceriotti; Filippo Martinelli-Boneschi; Flora Peyvandi; Francesco Blasi; Luis Tellez; Albert Blanco-Grau; Giacomo Grasselli; Giorgio Costantino; Giulia Cardamone; Giuseppe Foti; Serena Aneli; Hayato Kurihara; Hesham ElAbd; Ilaria My; Javier Martin; Jeanette Erdmann; Jose Ferrusquia-Acosta; Koldo Garcia-Etxebarria; Laura Izquierdo-Sanchez; Laura Rachele Bettini; Leonardo Terranova; Leticia Moreira; Luigi Santoro; Luigia Scudeller; Francisco Mesonero; Luisa Roade; Marco Schaefer; Maria Carrabba; Maria del Mar Riveiro Barciela; Maria Eloina Figuera Basso; Maria Grazia Valsecchi; Maria Hernandez-Tejero; Marialbert Acosta-Herrera; Mariella D'Angio; Marina Baldini; Marina Cazzaniga; Martin Schulzky; Maurizio Cecconi; Michael Wittig; Michele Ciccarelli; Miguel Rodriguez-Gandia; Monica Bocciolone; Monica Miozzo; Nicole Braun; Nilda Martinez; Orazio Palmieri; Paola Faverio; Paoletta Preatoni; Paolo Bonfanti; Paolo Omodei; Paolo Tentorio; Pedro Castro; Pedro M. Rodrigues; Aaron Blandino Ortiz; Ricardo Ferrer Roca; Roberta Gualtierotti; Rosa Nieto; Salvatore Badalamenti; Sara Marsal; Giuseppe Matullo; Serena Pelusi; Valter Monzani; Tanja Wesse; Tomas Pumarola; Valeria Rimoldi; Silvano Bosari; Wolfgang Albrecht; Wolfgang Peter; Manuel Romero Gomez; Mauro D'Amato; Stefano Duga; Jesus M. Banales; Johannes Roksund Hov; Trine Folseraas; Luca Valenti; Andre Franke; Tom Hemming Karlsen

    doi:10.1101/2020.05.31.20114991 Date: 2020-06-02 Source: medRxiv

    Background. Respiratory failure MESHD is a key feature of severe Covid-19 MESHD and a critical driver of mortality, but for reasons poorly defined affects less than 10% of SARS-CoV-2 infected MESHD patients. Methods. We included 1,980 patients with Covid-19 MESHD respiratory failure MESHD 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 meta-analysis 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<5x10-8) in the meta-analysis of both study panels, odds ratio [OR], 1.77; 95% confidence interval [CI], 1.48 to 2.11; P=1.14x10-10 and OR 1.32 HGNC (95% CI, 1.20 to 1.47; P=4.95x10-8), respectively. Among six genes at 3p21.31, SLC6A20 HGNC encodes a known interaction partner with angiotensin converting enzyme 2 HGNC ( ACE2 HGNC). The association signal at 9q34 was located at the ABO blood group HGNC 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=1.48x10-4) and a protective effect for blood group O (OR=0.65, 95% CI, 0.53 to 0.79, P=1.06x10-5). Conclusions. We herein report the first robust genetic susceptibility loci for the development of respiratory failure MESHD in Covid-19 MESHD. Identified variants may help guide targeted exploration of severe Covid-19 MESHD pathophysiology.

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MeSH Disease
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SARS-CoV-2 Proteins


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