Genomewide Association Study of Severe Covid-19 with Respiratory Failure

David Ellinghaus, Frauke Degenhardt, Luis Bujanda, Maria Buti, Agustín Albillos, Pietro Invernizzi, Javier Fernández, Daniele Prati, Guido Baselli, Rosanna Asselta, Marit M. Grimsrud, Chiara Milani, Fátima Aziz, Jan Kässens, Sandra May, Mareike Wendorff, Lars Wienbrandt, Florian Uellendahl-Werth, Tenghao Zheng, Xiaoli YiRaúl de Pablo, Adolfo G. Chercoles, Adriana Palom, Alba Estela Garcia-Fernandez, Francisco Rodriguez-Frias, Alberto Zanella, Alessandra Bandera, Alessandro Protti, Alessio Aghemo, Ana Lleo, Andrea Biondi, Andrea Caballero-Garralda, Andrea Gori, Anja Tanck, Anna Carreras Nolla, Anna Latiano, Anna Ludovica Fracanzani, Anna Peschuck, Antonio Julià, Antonio Pesenti, Antonio Voza, David Jiménez, Beatriz Mateos, Beatriz Nafria Jimenez, Carmen Quereda, Cinzia Paccapelo, Christoph Gassner, Claudio Angelini, Jeanette Erdmann, Severe Covid-19 GWAS Group, Siegfried Goerg

83 Citations (Scopus)


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 −8) 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 −10; and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P=4.95×10 −8, 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 −4) 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 −5). 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.

Original languageEnglish
JournalThe New England journal of medicine
Issue number16
Pages (from-to)1522-1534
Number of pages13
Publication statusPublished - 15.10.2020

Research Areas and Centers

  • Research Area: Medical Genetics
  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

Coronavirus related work

  • Research on SARS-CoV-2 / COVID-19


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