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 Yi; Raúl 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

doi:10.1056/NEJMoa2020283

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

University of Copenhagen, Denmark

83 Citations (Scopus)

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 ⁻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 language	English
Journal	The New England journal of medicine
Volume	383
Issue number	16
Pages (from-to)	1522-1534
Number of pages	13
ISSN	0028-4793
DOIs	https://doi.org/10.1056/NEJMoa2020283
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1056/NEJMoa2020283

Cite this

Ellinghaus, D., Degenhardt, F., Bujanda, L., Buti, M., Albillos, A., Invernizzi, P., Fernández, J., Prati, D., Baselli, G., Asselta, R., Grimsrud, M. M., Milani, C., Aziz, F., Kässens, J., May, S., Wendorff, M., Wienbrandt, L., Uellendahl-Werth, F., Zheng, T., ... Goerg, S. (2020). Genomewide Association Study of Severe Covid-19 with Respiratory Failure. The New England journal of medicine, 383(16), 1522-1534. https://doi.org/10.1056/NEJMoa2020283

@article{92443653f7664a9d9aee9e0467f8aa6d,

title = "Genomewide Association Study of Severe Covid-19 with Respiratory Failure",

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 −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. ",

author = "David Ellinghaus and Frauke Degenhardt and Luis Bujanda and Maria Buti and Agust{\'i}n Albillos and Pietro Invernizzi and Javier Fern{\'a}ndez and Daniele Prati and Guido Baselli and Rosanna Asselta and Grimsrud, {Marit M.} and Chiara Milani and F{\'a}tima Aziz and Jan K{\"a}ssens and Sandra May and Mareike Wendorff and Lars Wienbrandt and Florian Uellendahl-Werth and Tenghao Zheng and Xiaoli Yi and {de Pablo}, Ra{\'u}l and Chercoles, {Adolfo G.} and Adriana Palom and Garcia-Fernandez, {Alba Estela} and Francisco Rodriguez-Frias and Alberto Zanella and Alessandra Bandera and Alessandro Protti and Alessio Aghemo and Ana Lleo and Andrea Biondi and Andrea Caballero-Garralda and Andrea Gori and Anja Tanck and {Carreras Nolla}, Anna and Anna Latiano and Fracanzani, {Anna Ludovica} and Anna Peschuck and Antonio Juli{\`a} and Antonio Pesenti and Antonio Voza and David Jim{\'e}nez and Beatriz Mateos and {Nafria Jimenez}, Beatriz and Carmen Quereda and Cinzia Paccapelo and Christoph Gassner and Claudio Angelini and Jeanette Erdmann and {Severe Covid-19 GWAS Group} and Siegfried Goerg",

note = "Publisher Copyright: Copyright {\textcopyright} 2020 Massachusetts Medical Society.",

year = "2020",

month = oct,

day = "15",

doi = "10.1056/NEJMoa2020283",

language = "English",

volume = "383",

pages = "1522--1534",

journal = "The New England journal of medicine",

issn = "0028-4793",

number = "16",

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Ellinghaus, 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, Erdmann, J, Severe Covid-19 GWAS Group & Goerg, S 2020, 'Genomewide Association Study of Severe Covid-19 with Respiratory Failure', The New England journal of medicine, vol. 383, no. 16, pp. 1522-1534. https://doi.org/10.1056/NEJMoa2020283

TY - JOUR

T1 - Genomewide Association Study of Severe Covid-19 with Respiratory Failure

AU - Ellinghaus, David

AU - Degenhardt, Frauke

AU - Bujanda, Luis

AU - Buti, Maria

AU - Albillos, Agustín

AU - Invernizzi, Pietro

AU - Fernández, Javier

AU - Prati, Daniele

AU - Baselli, Guido

AU - Asselta, Rosanna

AU - Grimsrud, Marit M.

AU - Milani, Chiara

AU - Aziz, Fátima

AU - Kässens, Jan

AU - May, Sandra

AU - Wendorff, Mareike

AU - Wienbrandt, Lars

AU - Uellendahl-Werth, Florian

AU - Zheng, Tenghao

AU - Yi, Xiaoli

AU - de Pablo, Raúl

AU - Chercoles, Adolfo G.

AU - Palom, Adriana

AU - Garcia-Fernandez, Alba Estela

AU - Rodriguez-Frias, Francisco

AU - Zanella, Alberto

AU - Bandera, Alessandra

AU - Protti, Alessandro

AU - Aghemo, Alessio

AU - Lleo, Ana

AU - Biondi, Andrea

AU - Caballero-Garralda, Andrea

AU - Gori, Andrea

AU - Tanck, Anja

AU - Carreras Nolla, Anna

AU - Latiano, Anna

AU - Fracanzani, Anna Ludovica

AU - Peschuck, Anna

AU - Julià, Antonio

AU - Pesenti, Antonio

AU - Voza, Antonio

AU - Jiménez, David

AU - Mateos, Beatriz

AU - Nafria Jimenez, Beatriz

AU - Quereda, Carmen

AU - Paccapelo, Cinzia

AU - Gassner, Christoph

AU - Angelini, Claudio

AU - Erdmann, Jeanette

AU - Severe Covid-19 GWAS Group

AU - Goerg, Siegfried

PY - 2020/10/15

Y1 - 2020/10/15

N2 - 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.

AB - 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.

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UR - https://www.mendeley.com/catalogue/43ef4e18-ea84-3d0e-8783-559b44855674/

U2 - 10.1056/NEJMoa2020283

DO - 10.1056/NEJMoa2020283

M3 - Journal articles

C2 - 32558485

AN - SCOPUS:85087699779

SN - 0028-4793

VL - 383

SP - 1522

EP - 1534

JO - The New England journal of medicine

JF - The New England journal of medicine

IS - 16

ER -

Genomewide Association Study of Severe Covid-19 with Respiratory Failure

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Coronavirus related work

UN SDGs

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