We highlight in red genome-wide significant variants that had high heterogeneity across contributing studies and that were therefore excluded from the list of loci found. Loci highlighted in green (bottom) are regions associated with susceptibility to a SARS-CoV-2 infection-that is, the effect is the same across mild and severe COVID-19 phenotypes. Loci highlighted in yellow (top) represent regions associated with the severity of the COVID-19 manifestation-that is, increased odds of more severe COVID-19 phenotypes. Bottom, the results of reported SARS-CoV-2 infections ( n = 49,562 cases and n = 1,770,206 controls).
This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.Ī, Top, results of a genome-wide association study of hospitalized cases of COVID-19 ( n = 13,641 cases and n = 2,070,709 controls).
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. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. They also represent potentially actionable mechanisms in response to infection. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3-7. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. 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 formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. 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. 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. The genetic make-up of an individual contributes to the susceptibility and response to viral infection.
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