Mapping the human genetic architecture of COVID-19
COVID-19 Host Genetics Initiative, COVID-19 Host Genetics InitiativeLeadership, Mari Niemi, Juha Karjalainen, Rachel G. Liao, Benjamin M. Neale, Mark J. Daly, Andrea Ganna, Writing group, Writing group leaders, Gita A. Pathak, Shea J. Andrews, Masahiro Kanai, Writing group members, Kumar Veerapen, Israel Fernández‐Cadenas, Eva C. Schulte, Pasquale Striano, M. Marttila, Camelia C. Minică, Eirini Marouli, Mohd Anisul Karim, Frank R. Wendt, Jeanne E. 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, Analysis group, Manuscript analyses team leader, Manuscript analyses team member: meta-analysis, Juha Mehtonen, Manuscript analyses team member: heritability, methods and supplements, Manuscript analyses team member: PHEWAS, Manuscript analyses team member: Mendelian randomization, Manuscript analyses team member: PC projection and gene prioritization, Manuscript analyses team member: gene prioritization, Hilary K. Finucane, Manuscript analyses team member: sensitivity analysis, Mattia Cordioli, Manuscript analyses team members: PC projection, Alicia R. Martin, Wei Zhou, In silico analysis team members, Bogdan Paşaniuc, Hanna Julienne, Hugues Aschard, Huwenbo Shi, Loïc Yengo, Renato Polimanti, Maya Ghoussaini, Jeremy Schwartzentruber, Ian Dunham, Project management group, Project management leader, Project management support, Karolina Chwiałkowska, Margherita Francescatto, Amy Trankiem, Mary K. Balaconis, Phenotype steering group, Lea K. Davis, Sulggi A. Lee, James R. Priest, Alessandra Renieri, Vijay G. Sankaran, David A. van Heel, Patrick Deelen, J. Brent Richards, Tomoko Nakanishi, Les Biesecker, V. Eric Kerchberger, J. Kenneth Baillie, Data dictionary, Francesca Mari, Anna Bernasconi, J. Kenneth Baillie, Arif Canakoglu, Scientific communication group, Scientific communication leaders, Brooke Wolford, Scientific communication members, Annika Faucon, Atanu Kumar Dutta, Claudia Schurmann, Emi N. Harry, Ewan Birney, Huy Nguyen, Jamal Nasir, Mari Kaunisto, Matthew Solomonson, Nicole Dueker, Nirmal Vadgama
Abstract
Abstract 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 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 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.