Mapping the human genetic architecture of COVID-19
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Mapping the human genetic architecture of COVID-19. / Niemi, Mari E. K.; Karjalainen, Juha; Liao, Rachel G.; Neale, Benjamin M.; Daly, Mark; Ganna, Andrea; Pathak, Gita A.; Andrews, Shea J.; Kanai, Masahiro; Veerapen, Kumar; Fernandez-Cadenas, Israel; Schulte, Eva C.; Striano, Pasquale; Marttila, Minttu; Minica, Camelia; Marouli, Eirini; Karim, Mohd Anisul; Wendt, Frank R.; Savage, Jeanne; Sloofman, Laura; Butler-Laporte, Guillaume; Kim, Han-Na; Kanoni, Stavroula; Okada, Yukinori; Byun, Jinyoung; Han, Younghun; Uddin, Mohammed Jashim; Smith, George Davey; Willer, Cristen J.; Buxbaum, Joseph D.; Karjalainen, Juha; Mehtonen, Juha; Folkersen, Lasse; Moltke, Ida; Hinney, Anke; Wang, Chen; Ellinghaus, David; Brunak, Søren; Castro, Pedro; Guindo-Martinez, Marta; Lee, Ji Yeon; Loos, Ruth J. F.; Zhao, Jing Hua; Sun, Yan V.; Wang, Bo; Parker, Robert; Garcia, Sara Mingo; Smith, Oliver; Davis, Christopher; 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 Working.
In: Nature, Vol. 600, 2021, p. 472-477.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Mapping the human genetic architecture of COVID-19
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 - Karjalainen, Juha
AU - Mehtonen, Juha
AU - Folkersen, Lasse
AU - Moltke, Ida
AU - Hinney, Anke
AU - Wang, Chen
AU - Ellinghaus, David
AU - Brunak, Søren
AU - Castro, Pedro
AU - Guindo-Martinez, Marta
AU - Lee, Ji Yeon
AU - Loos, Ruth J. F.
AU - Zhao, Jing Hua
AU - Sun, Yan V.
AU - Wang, Bo
AU - Parker, Robert
AU - Garcia, Sara Mingo
AU - Smith, Oliver
AU - Davis, Christopher
AU - COVID-19 Host Genetics Initiative
AU - 23andMe COVID-19 Team
AU - Norwegian SARS-CoV-2 Study Grp
AU - Humanitas COVID-19 Task Force
AU - Humanitas Gavazzeni COVID-19 Task
AU - FHoGID
AU - RegCOVID
AU - P-PredictUs
AU - SeroCOVID
AU - CRiPSI
AU - Genes & Hlth Res Team
AU - UCLA Hlth ATLAS Data Mart Working
PY - 2021
Y1 - 2021
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-19(1,2), 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 across19 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 diseases(3-7). 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-19(1,2), 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 across19 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 diseases(3-7). 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.
KW - GENOME-WIDE ASSOCIATION
KW - SUSCEPTIBILITY LOCI
KW - HERITABILITY
KW - METAANALYSIS
U2 - 10.1038/s41586-021-03767-x
DO - 10.1038/s41586-021-03767-x
M3 - Journal article
C2 - 34237774
VL - 600
SP - 472
EP - 477
JO - Nature
JF - Nature
SN - 0028-0836
ER -
ID: 291675535