Mapping the human genetic architecture of COVID-19
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Niemi, Mari E. K.; Carnero Montoro, Elena; García García, Federico; Salazar, Adolfo de; Martín Ibáñez, Javier; Hernández Quero, José; Acosta Herrera, Marialbert; Chueca Porcuna, Natalia; González Cejudo, Trinidad; Alarcón Riquelme, Marta Eugenia; Martínez Bueno, Manuel; The COVID-19 Host Genetics Initiative; 23andMe COVID-19 Team; Norwegian SARS-CoV-2 Study Grp; Humanitas COVID-19 Task Force; Humanitas Gavazzeni COVID-19 Task; FHoGID; RegCOVID; P-PredictUs; SeroCOVID; CRiPSI; Genes & Hlth Res Team; UCLA Hlth ATLAS Data Mart WorkingEditorial
Nature
Date
2021-07-08Referencia bibliográfica
COVID-19 Host Genetics Initiative... [et al.]. Mapping the human genetic architecture of COVID-19. Nature 600, 472–477 (2021). [https://doi.org/10.1038/s41586-021-03767-x]
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.
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