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 -