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Mapping the human genetic architecture of COVID-19

COVID-19 Host Genetics Initiative, and Collins, CA (2021) Mapping the human genetic architecture of COVID-19. Nature, 600 (7889). 472-+. ISSN 0028-0836

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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
Uncontrolled Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; HERITABILITY; METAANALYSIS; 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; 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; General Science & Technology
Subjects: Q Science > Q Science (General)
Q Science > QC Physics
Q Science > QH Natural history > QH426 Genetics
Divisions: Astrophysics Research Institute
Publisher: Nature Publishing Group
SWORD Depositor: A Symplectic
Date Deposited: 17 Jun 2022 11:22
Last Modified: 17 Jun 2022 11:30
DOI or ID number: 10.1038/s41586-021-03767-x
URI: https://researchonline.ljmu.ac.uk/id/eprint/17105
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