Mapping the human genetic architecture of COVID-19

COVID-19 Host Genetics Initiative

doi:10.1038/s41586-021-03767-x

Mapping the human genetic architecture of COVID-19

COVID-19 Host Genetics Initiative

University of Helsinki
Harvard University
Broad Institute
Analytic and Translational Genetics Unit
Massachusetts General Hospital
Yale University
Icahn School of Medicine at Mount Sinai
Department of Biomedical Informatics
Program in Bioinformatics and Integrative Genomics
Stroke Pharmacogenomics and Genetics
Research Institute of Hospital de la Santa Creu i Sant Pau (IIB Sant Pau)
Institute of Virology
Technical University of Munich
Ludwig Maximilian University of Munich
Department of Psychiatry
IRCCS Istituto Giannina Gaslini - Genova
Department of Neurosciences
University of Genoa
Queen Mary University of London
Wellcome Genome Campus
Open Targets
Wellcome Trust Sanger Institute
Department of Complex Trait Genetics
Vrije Universiteit Amsterdam
Sir Mortimer B. Davis-Jewish General Hospital
Department of Epidemiology
McGill University
Medical Research Institute
Kangbuk Samsung Hospital
Department of Clinical Research Design and Evaluation
Sungkyunkwan University
The University of Osaka
Department of Statistical Genetics
Laboratory of Statistical Immunology
Integrated Frontier Research for Medical Science Division
Baylor College of Medicine
Mohammed Bin Rashid University of Medicine and Health Sciences
University of Bristol
University of Michigan, Ann Arbor
Department of Human Genetics
Department of Computational Medicine and Bioinformatics
Department of Psychiatry
University of California at Los Angeles
Human Genetics Department
Institut Pasteur Paris
University of Queensland
European Molecular Biology Laboratory
Centre for Bioinformatics and Data Analysis
Medical University of Białystok
University of Trieste
Qatar Foundation HQ

Research output: Contribution to journal › Article › peer-review

716 Citations (Scopus)

Abstract

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19^1,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases^3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

Original language	English
Pages (from-to)	472-477
Number of pages	6
Journal	Nature
Volume	600
Issue number	7889
DOIs	https://doi.org/10.1038/s41586-021-03767-x
Publication status	Published - 8 Jul 2021
Externally published	Yes

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10.1038/s41586-021-03767-x

Cite this

@article{e072b7c6cbab46ab864aeaeca4b15170,

title = "Mapping the human genetic architecture of COVID-19",

abstract = "The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3{\textendash}7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.",

author = "\{COVID-19 Host Genetics Initiative\} and Niemi, \{Mari E.K.\} and Juha Karjalainen and Liao, \{Rachel G.\} and Neale, \{Benjamin M.\} and Mark Daly and Andrea Ganna and Pathak, \{Gita A.\} and Andrews, \{Shea J.\} and Masahiro Kanai and Kumar Veerapen and Israel Fernandez-Cadenas and Schulte, \{Eva C.\} and Pasquale Striano and Minttu Marttila and Camelia Minica and Eirini Marouli and Karim, \{Mohd Anisul\} and Wendt, \{Frank R.\} and Jeanne Savage and Laura Sloofman and Guillaume Butler-Laporte and Kim, \{Han Na\} and Stavroula Kanoni and Yukinori Okada and Jinyoung Byun and Younghun Han and Uddin, \{Mohammed Jashim\} and Smith, \{George Davey\} and Willer, \{Cristen J.\} and Buxbaum, \{Joseph D.\} and Juha Mehtonen and Hilary Finucane and Mattia Cordioli and Martin, \{Alicia R.\} and Wei Zhou and Bogdan Pasaniuc and Hanna Julienne and Hugues Aschard and Huwenbo Shi and Loic Yengo and Renato Polimanti and Maya Ghoussaini and Jeremy Schwartzentruber and Ian Dunham and Karolina Chwialkowska and Margherita Francescatto and Amy Trankiem and Balaconis, \{Mary K.\} and Hottenga, \{Jouke Jan\} and Ismail, \{Said I.\}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = jul,

day = "8",

doi = "10.1038/s41586-021-03767-x",

language = "English",

volume = "600",

pages = "472--477",

journal = "Nature",

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number = "7889",

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T1 - Mapping the human genetic architecture of COVID-19

AU - COVID-19 Host Genetics Initiative

AU - Niemi, Mari E.K.

AU - Karjalainen, Juha

AU - Liao, Rachel G.

AU - Neale, Benjamin M.

AU - Daly, Mark

AU - Ganna, Andrea

AU - Pathak, Gita A.

AU - Andrews, Shea J.

AU - Kanai, Masahiro

AU - Veerapen, Kumar

AU - Fernandez-Cadenas, Israel

AU - Schulte, Eva C.

AU - Striano, Pasquale

AU - Marttila, Minttu

AU - Minica, Camelia

AU - Marouli, Eirini

AU - Karim, Mohd Anisul

AU - Wendt, Frank R.

AU - Savage, Jeanne

AU - Sloofman, Laura

AU - Butler-Laporte, Guillaume

AU - Kim, Han Na

AU - Kanoni, Stavroula

AU - Okada, Yukinori

AU - Byun, Jinyoung

AU - Han, Younghun

AU - Uddin, Mohammed Jashim

AU - Smith, George Davey

AU - Willer, Cristen J.

AU - Buxbaum, Joseph D.

AU - Mehtonen, Juha

AU - Finucane, Hilary

AU - Cordioli, Mattia

AU - Martin, Alicia R.

AU - Zhou, Wei

AU - Pasaniuc, Bogdan

AU - Julienne, Hanna

AU - Aschard, Hugues

AU - Shi, Huwenbo

AU - Yengo, Loic

AU - Polimanti, Renato

AU - Ghoussaini, Maya

AU - Schwartzentruber, Jeremy

AU - Dunham, Ian

AU - Chwialkowska, Karolina

AU - Francescatto, Margherita

AU - Trankiem, Amy

AU - Balaconis, Mary K.

AU - Hottenga, Jouke Jan

AU - Ismail, Said I.

PY - 2021/7/8

Y1 - 2021/7/8

N2 - The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

AB - The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

UR - https://www.scopus.com/pages/publications/85122771225

U2 - 10.1038/s41586-021-03767-x

DO - 10.1038/s41586-021-03767-x

M3 - Article

C2 - 34237774

AN - SCOPUS:85122771225

SN - 0028-0836

VL - 600

SP - 472

EP - 477

JO - Nature

JF - Nature

IS - 7889

ER -

Mapping the human genetic architecture of COVID-19

Abstract

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