TY - JOUR
T1 - Mapping the human genetic architecture of COVID-19
AU - COVID-19 Host Genetics Initiative
AU - Niemi, Mari E.K.
AU - Karjalainen, Juha
AU - Liao, Rachel G.
AU - Neale, Benjamin M.
AU - Daly, Mark
AU - Ganna, Andrea
AU - Pathak, Gita A.
AU - Andrews, Shea J.
AU - Kanai, Masahiro
AU - Veerapen, Kumar
AU - Fernandez-Cadenas, Israel
AU - Schulte, Eva C.
AU - Striano, Pasquale
AU - Marttila, Minttu
AU - Minica, Camelia
AU - Marouli, Eirini
AU - Karim, Mohd Anisul
AU - Wendt, Frank R.
AU - Savage, Jeanne
AU - Sloofman, Laura
AU - Butler-Laporte, Guillaume
AU - Kim, Han Na
AU - Kanoni, Stavroula
AU - Okada, Yukinori
AU - Byun, Jinyoung
AU - Han, Younghun
AU - Uddin, Mohammed Jashim
AU - Smith, George Davey
AU - Willer, Cristen J.
AU - Buxbaum, Joseph D.
AU - Mehtonen, Juha
AU - Finucane, Hilary
AU - Cordioli, Mattia
AU - Martin, Alicia R.
AU - Zhou, Wei
AU - Pasaniuc, Bogdan
AU - Julienne, Hanna
AU - Aschard, Hugues
AU - Shi, Huwenbo
AU - Yengo, Loic
AU - Polimanti, Renato
AU - Ghoussaini, Maya
AU - Schwartzentruber, Jeremy
AU - Dunham, Ian
AU - Chwialkowska, Karolina
AU - Francescatto, Margherita
AU - Trankiem, Amy
AU - Balaconis, Mary K.
AU - Davis, Lea
AU - O’Mahony, L.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/16
Y1 - 2021/12/16
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85122771225
U2 - 10.1038/s41586-021-03767-x
DO - 10.1038/s41586-021-03767-x
M3 - Article
C2 - 34237774
AN - SCOPUS:85122771225
SN - 0028-0836
VL - 600
SP - 472
EP - 477
JO - Nature
JF - Nature
IS - 7889
ER -
SDG 3 Good Health and Well-being