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An individual’s genetic makeup contributes to the susceptibility and response to viral infection. While environmental, clinical and social factors play a role in exposure to SARS-CoV-2 and severity of COVID-19 disease1.2, host genetics may also be important. Identification of host-specific genetic factors may reveal biological mechanisms of therapeutic importance and clarify the causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We have formed a global network of researchers to study the role of human genetics in SARS-CoV-2 infection and the severity of COVID-19. We describe the results of three meta-analyzes of genome-wide associations including up to 49,562 COVID-19 patients from 46 studies in 19 countries. We have reported 13 significant genome-wide loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations with pulmonary or autoimmune and inflammatory diseases.3–7. They also represent potentially actuable mechanisms in response to infection. Mendelian randomization analyzes support a causal role of smoking and body mass index for severe COVID-19, but not for type II diabetes. The identification of novel host genetic factors associated with COVID-19, at unprecedented speed, has been made possible by the community of human genetics researchers who have come together to prioritize the sharing of data, results, resources and analytical frameworks. This model of international collaborative work highlights what is possible for future genetic discoveries in emerging pandemics, or even for any complex human disease.
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