Genomewide Association Study of Severe Covid-19 with Respiratory Failure.

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. (Funded by Stein Erik Hagen and others.).

Copyright © 2020 Massachusetts Medical Society.

Overview publication

TitleGenomewide Association Study of Severe Covid-19 with Respiratory Failure.
Date2020-10-15
Issue nameThe New England journal of medicine
Issue numberv383.16:1522-1534
DOI10.1056/NEJMoa2020283
PubMed32558485
AuthorsEllinghaus D, Degenhardt F, Bujanda L, Buti M, Albillos A, Invernizzi P, Fernández J, Prati D, Baselli G, Asselta R, Grimsrud MM, Milani C, Aziz F, Kässens J, May S, Wendorff M, Wienbrandt L, Uellendahl-Werth F, Zheng T, Yi X, de Pablo R, Chercoles AG, Palom A, Garcia-Fernandez AE, Rodriguez-Frias F, Zanella A, Bandera A, Protti A, Aghemo A, Lleo A, Biondi A, Caballero-Garralda A, Gori A, Tanck A, Carreras Nolla A, Latiano A, Fracanzani AL, Peschuck A, Julià A, Pesenti A, Voza A, Jiménez D, Mateos B, Nafria Jimenez B, Quereda C, Paccapelo C, Gassner C, Angelini C, Cea C, Solier A, Pestaña D, Muñiz-Diaz E, Sandoval E, Paraboschi EM, Navas E, García Sánchez F, Ceriotti F, Martinelli-Boneschi F, Peyvandi F, Blasi F, Téllez L, Blanco-Grau A, Hemmrich-Stanisak G, Grasselli G, Costantino G, Cardamone G, Foti G, Aneli S, Kurihara H, ElAbd H, My I, Galván-Femenia I, Martín J, Erdmann J, Ferrusquía-Acosta J, Garcia-Etxebarria K, Izquierdo-Sanchez L, Bettini LR, Sumoy L, Terranova L, Moreira L, Santoro L, Scudeller L, Mesonero F, Roade L, Rühlemann MC, Schaefer M, Carrabba M, Riveiro-Barciela M, Figuera Basso ME, Valsecchi MG, Hernandez-Tejero M, Acosta-Herrera M, D'Angiò M, Baldini M, Cazzaniga M, Schulzky M, Cecconi M, Wittig M, Ciccarelli M, Rodríguez-Gandía M, Bocciolone M, Miozzo M, Montano N, Braun N, Sacchi N, Martínez N, Özer O, Palmieri O, Faverio P, Preatoni P, Bonfanti P, Omodei P, Tentorio P, Castro P, Rodrigues PM, Blandino Ortiz A, de Cid R, Ferrer R, Gualtierotti R, Nieto R, Goerg S, Badalamenti S, Marsal S, Matullo G, Pelusi S, Juzenas S, Aliberti S, Monzani V, Moreno V, Wesse T, Lenz TL, Pumarola T, Rimoldi V, Bosari S, Albrecht W, Peter W, Romero-Gómez M, D'Amato M, Duga S, Banales JM, Hov JR, Folseraas T, Valenti L, Franke A & Karlsen TH
InfoSevere Covid-19 GWAS Group, Aghemo A, Angelini C, Badalamenti S, Balzarini L, Bocciolone M, Cecconi M, Ciccarelli M, Kurihara H, Lagioia M, Omodei P, Preatoni P, Voza A, Accornero S, Alfarone L, Ali H, Arcari I, Arosio P, Azzolini E, Baccarin A, Baggio S, Barbagallo M, Barberi C, Barbic F, Barbieri V, Barbone A, Basciu A, Benvenuti C, Bianchi I, Bombace S, Borea F, Borroni M, Bresciani G, Brunetta E, Bulletti C, Cadonati C, Calabro' L, Calatroni M, Calvetta AA, Cannata F, Canziani L, Capogreco A, Capretti GL, Carlani E, Carrone F, Casana M, Ceribelli A, Ceriotti C, Cimino M, Ciuffini L, Colaizzi C, Colapietro F, Costa G, Cozzi O, Craviotto V, Crespi C, Crippa M, Da Rio L, Dal Farra S, D'antonio F, De Ambroggi G, De Donato M, De Lucia F, De Nittis P, De Santis M, Delle Rose G, Di Pilla M, Dipaola F, Dipasquale A, Dipasquale A, Droandi G, Fazio R, Ferrante G, Ferrara EC, Ferrari MC, Ferri S, Folci M, Foresti S, Franchi E, Fraolini E, Furfaro F, Galimberti P, Galtieri A, Gavazzi F, Generali E, Goletti B, Guidelli G, Jacobs F, Gherardo LA, Libre' L, Lleo A, Loiacono F, Lughezzani G, Maccallini M, Magnoni P, Maiorino AF, Malesci A, Mantovani R, Marchettini D, Marinello A, Markopoulos N, Masetti C, Mazziotti G, Milani A, Mirani M, Morelli P, Motta F, Mundula V, Nigro M, Ormas M, Pagliaro A, Paliotti R, Pavesi A, Pedale R, Pegoraro F, Pellegatta G, Pellegrino M, Petriello G, Piccini S, Pocaterra D, Poliani L, Procopio F, Puggioni F, Pugliese L, Pugliese N, Racca F, Randazzo M, Regazzoli LD, Reggiani F, Rimoldi M, Rodolfi S, Ruongo L, Sacco C, Sagasta M, Sandri MT, Savi M, Scarfo' I, Shiffer D, Sicoli F, Solano S, Solitano V, Spata G, Stainer A, Stella MC, Strangio G, Taormina A, Testoni L, Tordato F, Trabucco A, Ulian L, Valentino R, Valeriano C, Vena W, Verlingieri S, Vespa E, Zanon Z, Veronica V, Zanuso V, Zilli A, Lutman F, Lanza E, Profili M, Giannitto C, Mrakic Sposta F, Torrisi C, Poretti D, Pedicini V, Bonifacio C, D'orazio F, D'antuono F, Castelli A, Pestalozza A, Paiardi S, Teofilo FI, Citterio G, Aloise M, Ripoll Pons M, Lavezzi E, Fedeli C, Desai A, Caltagirone G, Voza G, Giorgino MG, Lude F, Boezen MH, Deelen P, Claringbould A, Lopera-Maya EA, van Heel DA, Trivedi B, Hunt KA, MacLaughlin B, Huang Q, Martin HC, Trembath RC, Griffiths C, Finer S, Wright J, Mason D, Moscati A, Cho JH, Loos RJF, Cirulli ET, Schiabor Barrett KM, Riffle S, Bolze A, White S, Tanudjaja F, Wang X, Ramirez JM, Lim YW, Washington NL, Lu JT, de Geus E, Bartels M, Hottenga JJ, Wilson DJ, Arning N, Armstrong J, Rudkin J, Band G, Earle SG, Lin SK, Crook DW, Wyllie DH, O'Connell AM, Nakanishi T, Forgetta V, Butler-Laporte G, Richards JB, Karczewski KJ, Atkinson EG, Kanai M, Baya N, Turley P, Walters RK, Palmer DS, Bryant S, Churchhouse C, Finucane H, Martin AR, Weiss S, Karlson EW, Smoller JW, Slaugenhaupt SA, Green R, Feng YA, Mercader JM, Murphy SN, Meigs JB, Woolley A, Perez E, Chwialkowska K, Francescatto M, Trankiem A, Solomonson M, Liao R, Nguyen H, Karjalainen J, Zhou W
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