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Mapping the human genetic architecture of COVID-19.

COVID-19 Host Genetics Initiative (2021) Mapping the human genetic architecture of COVID-19. Nature, 600 (7889). pp. 472-477. ISSN 1476-4687 https://doi.org/10.1038/s41586-021-03767-x
SGUL Authors: Cosgrove, Catherine

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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 diseases3-7. 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.

Item Type: Article
Additional Information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2021
Keywords: Autoimmunity, Body Mass Index, COVID-19, Critical Illness, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Geographic Mapping, Hospitalization, Host-Pathogen Interactions, Humans, Inflammation, Information Dissemination, Male, Multifactorial Inheritance, Racial Groups, SARS-CoV-2, Smoking, COVID-19 Host Genetics Initiative, Humans, Critical Illness, Genetic Predisposition to Disease, Inflammation, Body Mass Index, Hospitalization, Information Dissemination, Smoking, Autoimmunity, Multifactorial Inheritance, Female, Male, Host-Pathogen Interactions, Genome-Wide Association Study, Genetic Loci, Geographic Mapping, COVID-19, SARS-CoV-2, Racial Groups, General Science & Technology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Nature
ISSN: 1476-4687
Language: eng
Dates:
DateEvent
December 2021Published
8 July 2021Published Online
23 June 2021Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
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MR/K01417X/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
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MR/P011705/2Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MR/N02995X/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MC_PC_20004Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
R01 HG009120NHGRI NIH HHSUNSPECIFIED
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MC_PC_19059Medical Research CouncilUNSPECIFIED
T32 HG000040NHGRI NIH HHSUNSPECIFIED
MR/R026408/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MC_UU_00011/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G-1307Parkinson's UKhttp://dx.doi.org/10.13039/501100000304
F31 MH124306NIMH NIH HHSUNSPECIFIED
K01 MH121659NIMH NIH HHSUNSPECIFIED
MR/S006753/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
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MR/J004758/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MC_UU_00007/10Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MC_UU_12014/8Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MC_PC_19025Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MR/P011705/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
PubMed ID: 34237774
Web of Science ID: WOS:000723539300001
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/114687
Publisher's version: https://doi.org/10.1038/s41586-021-03767-x

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