Mapping the human genetic architecture of COVID-19

Covid-19 Host Genetics Initiative , Mari E K Niemi (1) , Juha Karjalainen (1) , Rachel G Liao (2) , Benjamin M Neale (2, 3) , Mark Daly (1, 2, 3) , Andrea Ganna (1, 2, 3) , Gita A Pathak , Shea J Andrews , Masahiro Kanai , Kumar Veerapen , Israel Fernandez-Cadenas , Eva C Schulte , Pasquale Striano , Minttu Marttila , Camelia Minica , Eirini Marouli , Anisul Karim , Frank R Wendt , Jeanne Savage , Laura Sloofman , Guillaume Butler-Laporte , Han-Na Kim , Stavroula Kanoni , Yukinori Okada , Jinyoung Byun , Younghun Han , Mohammed Jashim Uddin , George Davey Smith , Cristen J Willer , Joseph D Buxbaum

1 FIMM - Institute for Molecular Medicine Finland [Helsinki]
2 BROAD INSTITUTE - Broad Institute of MIT and Harvard
3 Massachusetts General Hospital [Boston]

The genetic makeup of an individual contributes to susceptibility and response to viral infection. While environmental, clinical and social factors play a role in exposure to SARS-CoV-2 and COVID-19 disease severity1,2, 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. We describe the results of three genome-wide association meta-analyses comprised of up to 49,562 COVID-19 patients from 46 studies across 19 countries. We reported 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, with unprecedented speed, was made possible by the community of human genetic researchers coming together to prioritize 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.

Domains: Genetics; Infectious diseases

Covid-19 Host Genetics Initiative, Mari E K Niemi, Juha Karjalainen, Rachel G Liao, Benjamin M Neale, et al.. Mapping the human genetic architecture of COVID-19. Nature, 2021, 600 (7889), pp.472-477. ⟨10.1038/s41586-021-03767-x⟩. ⟨pasteur-03282354⟩