tetano
Editor, Senior Moderator
N Engl J Med
. 2020 Jun 17.
doi: 10.1056/NEJMoa2020283. Online ahead of print.
Genomewide Association Study of Severe Covid-19 With Respiratory Failure
David Ellinghaus[SUP] 1 [/SUP], Frauke Degenhardt[SUP] 1 [/SUP], Luis Bujanda[SUP] 1 [/SUP], Maria Buti[SUP] 1 [/SUP], Agust?n Albillos[SUP] 1 [/SUP], Pietro Invernizzi[SUP] 1 [/SUP], Javier Fern?ndez[SUP] 1 [/SUP], Daniele Prati[SUP] 1 [/SUP], Guido Baselli[SUP] 1 [/SUP], Rosanna Asselta[SUP] 1 [/SUP], Marit M Grimsrud[SUP] 1 [/SUP], Chiara Milani[SUP] 1 [/SUP], F?tima Aziz[SUP] 1 [/SUP], Jan K?ssens[SUP] 1 [/SUP], Sandra May[SUP] 1 [/SUP], Mareike Wendorff[SUP] 1 [/SUP], Lars Wienbrandt[SUP] 1 [/SUP], Florian Uellendahl-Werth[SUP] 1 [/SUP], Tenghao Zheng[SUP] 1 [/SUP], Xiaoli Yi[SUP] 1 [/SUP], Ra?l de Pablo[SUP] 1 [/SUP], Adolfo G Chercoles[SUP] 1 [/SUP], Adriana Palom[SUP] 1 [/SUP], Alba-Estela Garcia-Fernandez[SUP] 1 [/SUP], Francisco Rodriguez-Frias[SUP] 1 [/SUP], Alberto Zanella[SUP] 1 [/SUP], Alessandra Bandera[SUP] 1 [/SUP], Alessandro Protti[SUP] 1 [/SUP], Alessio Aghemo[SUP] 1 [/SUP], Ana Lleo[SUP] 1 [/SUP], Andrea Biondi[SUP] 1 [/SUP], Andrea Caballero-Garralda[SUP] 1 [/SUP], Andrea Gori[SUP] 1 [/SUP], Anja Tanck[SUP] 1 [/SUP], Anna Carreras Nolla[SUP] 1 [/SUP], Anna Latiano[SUP] 1 [/SUP], Anna Ludovica Fracanzani[SUP] 1 [/SUP], Anna Peschuck[SUP] 1 [/SUP], Antonio Juli?[SUP] 1 [/SUP], Antonio Pesenti[SUP] 1 [/SUP], Antonio Voza[SUP] 1 [/SUP], David Jim?nez[SUP] 1 [/SUP], Beatriz Mateos[SUP] 1 [/SUP], Beatriz Nafria Jimenez[SUP] 1 [/SUP], Carmen Quereda[SUP] 1 [/SUP], Cinzia Paccapelo[SUP] 1 [/SUP], Christoph Gassner[SUP] 1 [/SUP], Claudio Angelini[SUP] 1 [/SUP], Cristina Cea[SUP] 1 [/SUP], Aurora Solier[SUP] 1 [/SUP], David Pesta?a[SUP] 1 [/SUP], Eduardo Mu?iz-Diaz[SUP] 1 [/SUP], Elena Sandoval[SUP] 1 [/SUP], Elvezia M Paraboschi[SUP] 1 [/SUP], Enrique Navas[SUP] 1 [/SUP], F?lix Garc?a S?nchez[SUP] 1 [/SUP], Ferruccio Ceriotti[SUP] 1 [/SUP], Filippo Martinelli-Boneschi[SUP] 1 [/SUP], Flora Peyvandi[SUP] 1 [/SUP], Francesco Blasi[SUP] 1 [/SUP], Luis T?llez[SUP] 1 [/SUP], Albert Blanco-Grau[SUP] 1 [/SUP], Georg Hemmrich-Stanisak[SUP] 1 [/SUP], Giacomo Grasselli[SUP] 1 [/SUP], Giorgio Costantino[SUP] 1 [/SUP], Giulia Cardamone[SUP] 1 [/SUP], Giuseppe Foti[SUP] 1 [/SUP], Serena Aneli[SUP] 1 [/SUP], Hayato Kurihara[SUP] 1 [/SUP], Hesham ElAbd[SUP] 1 [/SUP], Ilaria My[SUP] 1 [/SUP], Iv?n Galv?n-Femenia[SUP] 1 [/SUP], Javier Mart?n[SUP] 1 [/SUP], Jeanette Erdmann[SUP] 1 [/SUP], Jose Ferrusqu?a-Acosta[SUP] 1 [/SUP], Koldo Garcia-Etxebarria[SUP] 1 [/SUP], Laura Izquierdo-Sanchez[SUP] 1 [/SUP], Laura R Bettini[SUP] 1 [/SUP], Lauro Sumoy[SUP] 1 [/SUP], Leonardo Terranova[SUP] 1 [/SUP], Leticia Moreira[SUP] 1 [/SUP], Luigi Santoro[SUP] 1 [/SUP], Luigia Scudeller[SUP] 1 [/SUP], Francisco Mesonero[SUP] 1 [/SUP], Luisa Roade[SUP] 1 [/SUP], Malte C R?hlemann[SUP] 1 [/SUP], Marco Schaefer[SUP] 1 [/SUP], Maria Carrabba[SUP] 1 [/SUP], Mar Riveiro-Barciela[SUP] 1 [/SUP], Maria E Figuera Basso[SUP] 1 [/SUP], Maria G Valsecchi[SUP] 1 [/SUP], Mar?a Hernandez-Tejero[SUP] 1 [/SUP], Marialbert Acosta-Herrera[SUP] 1 [/SUP], Mariella D'Angi?[SUP] 1 [/SUP], Marina Baldini[SUP] 1 [/SUP], Marina Cazzaniga[SUP] 1 [/SUP], Martin Schulzky[SUP] 1 [/SUP], Maurizio Cecconi[SUP] 1 [/SUP], Michael Wittig[SUP] 1 [/SUP], Michele Ciccarelli[SUP] 1 [/SUP], Miguel Rodr?guez-Gand?a[SUP] 1 [/SUP], Monica Bocciolone[SUP] 1 [/SUP], Monica Miozzo[SUP] 1 [/SUP], Nicola Montano[SUP] 1 [/SUP], Nicole Braun[SUP] 1 [/SUP], Nicoletta Sacchi[SUP] 1 [/SUP], Nilda Mart?nez[SUP] 1 [/SUP], Onur ?zer[SUP] 1 [/SUP], Orazio Palmieri[SUP] 1 [/SUP], Paola Faverio[SUP] 1 [/SUP], Paoletta Preatoni[SUP] 1 [/SUP], Paolo Bonfanti[SUP] 1 [/SUP], Paolo Omodei[SUP] 1 [/SUP], Paolo Tentorio[SUP] 1 [/SUP], Pedro Castro[SUP] 1 [/SUP], Pedro M Rodrigues[SUP] 1 [/SUP], Aaron Blandino Ortiz[SUP] 1 [/SUP], Rafael de Cid[SUP] 1 [/SUP], Ricard Ferrer[SUP] 1 [/SUP], Roberta Gualtierotti[SUP] 1 [/SUP], Rosa Nieto[SUP] 1 [/SUP], Siegfried Goerg[SUP] 1 [/SUP], Salvatore Badalamenti[SUP] 1 [/SUP], Sara Marsal[SUP] 1 [/SUP], Giuseppe Matullo[SUP] 1 [/SUP], Serena Pelusi[SUP] 1 [/SUP], Simonas Juzenas[SUP] 1 [/SUP], Stefano Aliberti[SUP] 1 [/SUP], Valter Monzani[SUP] 1 [/SUP], Victor Moreno[SUP] 1 [/SUP], Tanja Wesse[SUP] 1 [/SUP], Tobias L Lenz[SUP] 1 [/SUP], Tomas Pumarola[SUP] 1 [/SUP], Valeria Rimoldi[SUP] 1 [/SUP], Silvano Bosari[SUP] 1 [/SUP], Wolfgang Albrecht[SUP] 1 [/SUP], Wolfgang Peter[SUP] 1 [/SUP], Manuel Romero-G?mez[SUP] 1 [/SUP], Mauro D'Amato[SUP] 1 [/SUP], Stefano Duga[SUP] 1 [/SUP], Jesus M Banales[SUP] 1 [/SUP], Johannes R Hov[SUP] 1 [/SUP], Trine Folseraas[SUP] 1 [/SUP], Luca Valenti[SUP] 1 [/SUP], Andre Franke[SUP] 1 [/SUP], Tom H Karlsen[SUP] 1 [/SUP], Severe Covid-19 GWAS Group
Affiliations
Abstract
Background: There is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19.
Methods: We conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality control and the exclusion of population outliers, 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case-control panels.
Results: We detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level (P<5?10[SUP]-8[/SUP]) in the meta-analysis of the two case-control panels (odds ratio, 1.77; 95% confidence interval [CI], 1.48 to 2.11; P = 1.15?10[SUP]-10[/SUP]; and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P = 4.95?10[SUP]-8[/SUP], respectively). At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-group-specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P = 1.48?10[SUP]-4[/SUP]) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P = 1.06?10[SUP]-5[/SUP]).
Conclusions: We identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system. (Funded by Stein Erik Hagen and others.).
. 2020 Jun 17.
doi: 10.1056/NEJMoa2020283. Online ahead of print.
Genomewide Association Study of Severe Covid-19 With Respiratory Failure
David Ellinghaus[SUP] 1 [/SUP], Frauke Degenhardt[SUP] 1 [/SUP], Luis Bujanda[SUP] 1 [/SUP], Maria Buti[SUP] 1 [/SUP], Agust?n Albillos[SUP] 1 [/SUP], Pietro Invernizzi[SUP] 1 [/SUP], Javier Fern?ndez[SUP] 1 [/SUP], Daniele Prati[SUP] 1 [/SUP], Guido Baselli[SUP] 1 [/SUP], Rosanna Asselta[SUP] 1 [/SUP], Marit M Grimsrud[SUP] 1 [/SUP], Chiara Milani[SUP] 1 [/SUP], F?tima Aziz[SUP] 1 [/SUP], Jan K?ssens[SUP] 1 [/SUP], Sandra May[SUP] 1 [/SUP], Mareike Wendorff[SUP] 1 [/SUP], Lars Wienbrandt[SUP] 1 [/SUP], Florian Uellendahl-Werth[SUP] 1 [/SUP], Tenghao Zheng[SUP] 1 [/SUP], Xiaoli Yi[SUP] 1 [/SUP], Ra?l de Pablo[SUP] 1 [/SUP], Adolfo G Chercoles[SUP] 1 [/SUP], Adriana Palom[SUP] 1 [/SUP], Alba-Estela Garcia-Fernandez[SUP] 1 [/SUP], Francisco Rodriguez-Frias[SUP] 1 [/SUP], Alberto Zanella[SUP] 1 [/SUP], Alessandra Bandera[SUP] 1 [/SUP], Alessandro Protti[SUP] 1 [/SUP], Alessio Aghemo[SUP] 1 [/SUP], Ana Lleo[SUP] 1 [/SUP], Andrea Biondi[SUP] 1 [/SUP], Andrea Caballero-Garralda[SUP] 1 [/SUP], Andrea Gori[SUP] 1 [/SUP], Anja Tanck[SUP] 1 [/SUP], Anna Carreras Nolla[SUP] 1 [/SUP], Anna Latiano[SUP] 1 [/SUP], Anna Ludovica Fracanzani[SUP] 1 [/SUP], Anna Peschuck[SUP] 1 [/SUP], Antonio Juli?[SUP] 1 [/SUP], Antonio Pesenti[SUP] 1 [/SUP], Antonio Voza[SUP] 1 [/SUP], David Jim?nez[SUP] 1 [/SUP], Beatriz Mateos[SUP] 1 [/SUP], Beatriz Nafria Jimenez[SUP] 1 [/SUP], Carmen Quereda[SUP] 1 [/SUP], Cinzia Paccapelo[SUP] 1 [/SUP], Christoph Gassner[SUP] 1 [/SUP], Claudio Angelini[SUP] 1 [/SUP], Cristina Cea[SUP] 1 [/SUP], Aurora Solier[SUP] 1 [/SUP], David Pesta?a[SUP] 1 [/SUP], Eduardo Mu?iz-Diaz[SUP] 1 [/SUP], Elena Sandoval[SUP] 1 [/SUP], Elvezia M Paraboschi[SUP] 1 [/SUP], Enrique Navas[SUP] 1 [/SUP], F?lix Garc?a S?nchez[SUP] 1 [/SUP], Ferruccio Ceriotti[SUP] 1 [/SUP], Filippo Martinelli-Boneschi[SUP] 1 [/SUP], Flora Peyvandi[SUP] 1 [/SUP], Francesco Blasi[SUP] 1 [/SUP], Luis T?llez[SUP] 1 [/SUP], Albert Blanco-Grau[SUP] 1 [/SUP], Georg Hemmrich-Stanisak[SUP] 1 [/SUP], Giacomo Grasselli[SUP] 1 [/SUP], Giorgio Costantino[SUP] 1 [/SUP], Giulia Cardamone[SUP] 1 [/SUP], Giuseppe Foti[SUP] 1 [/SUP], Serena Aneli[SUP] 1 [/SUP], Hayato Kurihara[SUP] 1 [/SUP], Hesham ElAbd[SUP] 1 [/SUP], Ilaria My[SUP] 1 [/SUP], Iv?n Galv?n-Femenia[SUP] 1 [/SUP], Javier Mart?n[SUP] 1 [/SUP], Jeanette Erdmann[SUP] 1 [/SUP], Jose Ferrusqu?a-Acosta[SUP] 1 [/SUP], Koldo Garcia-Etxebarria[SUP] 1 [/SUP], Laura Izquierdo-Sanchez[SUP] 1 [/SUP], Laura R Bettini[SUP] 1 [/SUP], Lauro Sumoy[SUP] 1 [/SUP], Leonardo Terranova[SUP] 1 [/SUP], Leticia Moreira[SUP] 1 [/SUP], Luigi Santoro[SUP] 1 [/SUP], Luigia Scudeller[SUP] 1 [/SUP], Francisco Mesonero[SUP] 1 [/SUP], Luisa Roade[SUP] 1 [/SUP], Malte C R?hlemann[SUP] 1 [/SUP], Marco Schaefer[SUP] 1 [/SUP], Maria Carrabba[SUP] 1 [/SUP], Mar Riveiro-Barciela[SUP] 1 [/SUP], Maria E Figuera Basso[SUP] 1 [/SUP], Maria G Valsecchi[SUP] 1 [/SUP], Mar?a Hernandez-Tejero[SUP] 1 [/SUP], Marialbert Acosta-Herrera[SUP] 1 [/SUP], Mariella D'Angi?[SUP] 1 [/SUP], Marina Baldini[SUP] 1 [/SUP], Marina Cazzaniga[SUP] 1 [/SUP], Martin Schulzky[SUP] 1 [/SUP], Maurizio Cecconi[SUP] 1 [/SUP], Michael Wittig[SUP] 1 [/SUP], Michele Ciccarelli[SUP] 1 [/SUP], Miguel Rodr?guez-Gand?a[SUP] 1 [/SUP], Monica Bocciolone[SUP] 1 [/SUP], Monica Miozzo[SUP] 1 [/SUP], Nicola Montano[SUP] 1 [/SUP], Nicole Braun[SUP] 1 [/SUP], Nicoletta Sacchi[SUP] 1 [/SUP], Nilda Mart?nez[SUP] 1 [/SUP], Onur ?zer[SUP] 1 [/SUP], Orazio Palmieri[SUP] 1 [/SUP], Paola Faverio[SUP] 1 [/SUP], Paoletta Preatoni[SUP] 1 [/SUP], Paolo Bonfanti[SUP] 1 [/SUP], Paolo Omodei[SUP] 1 [/SUP], Paolo Tentorio[SUP] 1 [/SUP], Pedro Castro[SUP] 1 [/SUP], Pedro M Rodrigues[SUP] 1 [/SUP], Aaron Blandino Ortiz[SUP] 1 [/SUP], Rafael de Cid[SUP] 1 [/SUP], Ricard Ferrer[SUP] 1 [/SUP], Roberta Gualtierotti[SUP] 1 [/SUP], Rosa Nieto[SUP] 1 [/SUP], Siegfried Goerg[SUP] 1 [/SUP], Salvatore Badalamenti[SUP] 1 [/SUP], Sara Marsal[SUP] 1 [/SUP], Giuseppe Matullo[SUP] 1 [/SUP], Serena Pelusi[SUP] 1 [/SUP], Simonas Juzenas[SUP] 1 [/SUP], Stefano Aliberti[SUP] 1 [/SUP], Valter Monzani[SUP] 1 [/SUP], Victor Moreno[SUP] 1 [/SUP], Tanja Wesse[SUP] 1 [/SUP], Tobias L Lenz[SUP] 1 [/SUP], Tomas Pumarola[SUP] 1 [/SUP], Valeria Rimoldi[SUP] 1 [/SUP], Silvano Bosari[SUP] 1 [/SUP], Wolfgang Albrecht[SUP] 1 [/SUP], Wolfgang Peter[SUP] 1 [/SUP], Manuel Romero-G?mez[SUP] 1 [/SUP], Mauro D'Amato[SUP] 1 [/SUP], Stefano Duga[SUP] 1 [/SUP], Jesus M Banales[SUP] 1 [/SUP], Johannes R Hov[SUP] 1 [/SUP], Trine Folseraas[SUP] 1 [/SUP], Luca Valenti[SUP] 1 [/SUP], Andre Franke[SUP] 1 [/SUP], Tom H Karlsen[SUP] 1 [/SUP], Severe Covid-19 GWAS Group
Affiliations
- PMID: 32558485
- DOI: 10.1056/NEJMoa2020283
Abstract
Background: There is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19.
Methods: We conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality control and the exclusion of population outliers, 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case-control panels.
Results: We detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level (P<5?10[SUP]-8[/SUP]) in the meta-analysis of the two case-control panels (odds ratio, 1.77; 95% confidence interval [CI], 1.48 to 2.11; P = 1.15?10[SUP]-10[/SUP]; and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P = 4.95?10[SUP]-8[/SUP], respectively). At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-group-specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P = 1.48?10[SUP]-4[/SUP]) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P = 1.06?10[SUP]-5[/SUP]).
Conclusions: We identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system. (Funded by Stein Erik Hagen and others.).