Mapping the human genetic architecture of COVID-19

Mari E.K. Niemi; Juha Karjalainen; Rachel G. Liao; Benjamin M. Neale; Mark Daly; Andrea Ganna; Gita A. Pathak; Shea J. Andrews; Masahiro Kanai; Kumar Veerapen; Israel Fernandez-Cadenas; Eva C. Schulte; Pasquale Striano; Minttu Marttila; Camelia Minica; Eirini Marouli; Mohd 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; Juha Mehtonen; Hilary Finucane; Mattia Cordioli; Alicia R. Martin; Wei Zhou; Bogdan Pasaniuc; Hanna Julienne; Hugues Aschard; Huwenbo Shi; Loic Yengo; Renato Polimanti; Maya Ghoussaini; Jeremy Schwartzentruber; Ian Dunham; Karolina Chwialkowska; Margherita Francescatto; Amy Trankiem; Mary K. Balaconis; Lea Davis; Julian L. Griffin; COVID-19 Host Genetics Initiative

doi:10.1038/s41586-021-03767-x

Mapping the human genetic architecture of COVID-19

Mari E.K. Niemi, Juha Karjalainen, Rachel G. Liao, Benjamin M. Neale^* (Corresponding Author), Mark Daly^* (Corresponding Author), Andrea Ganna^* (Corresponding Author), Gita A. Pathak, Shea J. Andrews, Masahiro Kanai, Kumar Veerapen, Israel Fernandez-Cadenas, Eva C. Schulte, Pasquale Striano, Minttu Marttila, Camelia Minica, Eirini Marouli, Mohd Anisul Karim, Frank R. Wendt, Jeanne Savage, Laura SloofmanGuillaume 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, Juha Mehtonen, Hilary Finucane, Mattia Cordioli, Alicia R. Martin, Wei Zhou, Bogdan Pasaniuc, Hanna Julienne, Hugues Aschard, Huwenbo Shi, Loic Yengo, Renato Polimanti, Maya Ghoussaini, Jeremy Schwartzentruber, Ian Dunham, Karolina Chwialkowska, Margherita Francescatto, Amy Trankiem, Mary K. Balaconis, Lea Davis, Julian L. Griffin, COVID-19 Host Genetics Initiative

^*Corresponding author for this work

The Rowett Institute of Nutrition and Health

Research output: Contribution to journal › Article › peer-review

481 Citations (Scopus)

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.

Original language	English
Pages (from-to)	472-477
Number of pages	6
Journal	Nature
Volume	600
Issue number	7889
Early online date	8 Jul 2021
DOIs	https://doi.org/10.1038/s41586-021-03767-x
Publication status	Published - 8 Jul 2021

Bibliographical note

We thank the entire COVID-19 HGI community for their contributions and continued collaboration. The work of the contributing studies was supported by numerous grants from governmental and charitable bodies. Acknowledgements specific to contributing studies are provided in Supplementary Table 13. We thank G. Butler-Laporte, G. Wojcik, M.-G. Hollm-Delgado, C. Willer and G. Davey Smith for their extensive feedback and discussion.

Erratum to: Mapping the human genetic architecture of COVID-19 (Nature, (2021), 600, 7889, (472-477), 10.1038/s41586-021-03767-x)
Mari E.K. Niemi, Juha Karjalainen, Rachel G. Liao, Benjamin M. Neale, Mark Daly, Andrea Ganna, Gita A. Pathak, Shea J. Andrews, Masahiro Kanai, Kumar Veerapen, Israel Fernandez-Cadenas, Eva C. Schulte, Pasquale Striano, Minttu Marttila, Camelia Minica, Eirini Marouli, Mohd Anisul Karim, Frank R. Wendt, Jeanne Savage, Laura Sloofman, 2023, vol. 621, issue 7977, p. E7-E26. Nature https://doi.org/10.1093/1476-4687

Data Availability Statement

Summary statistics generated by COVID-19 HGI are available at https://www.covid19hg.org/results/r5/ and are available on GWAS Catalog (study code GCST011074). The analyses described here utilize the freeze 5 data. COVID-19 HGI continues to regularly release new data freezes. Summary statistics for nonEuropean ancestry samples are not currently available due to the small individual sample sizes of these groups, but results for 13 loci lead variants are reported in Supplementary Table 3. Individual level data can be requested directly from contributing studies, listed in Supplementary Table 1. We used publicly available data from GTEx (https://gtexportal.org/home/), the Neale lab (http://www.nealelab.is/uk-biobank/), Finucane lab (https://www.finucanelab.org), FinnGen Freeze 4 cohort (https://www.finngen.fi/en/access_results), and eQTL catalogue release 3 (http://www.ebi.ac.uk/eqtl/).

Any methods, additional references, Nature Research reporting summaries, source data, extended data, supplementary information, acknowledgements, peer review information; details of author contributions and competing interests; and statements of data and code availability are available at https://doi.org/10.1038/s41586-021-03767-x.

Keywords

Autoimmunity/genetics
Body Mass Index
COVID-19/genetics
Critical Illness
Female
Genetic Loci/genetics
Genetic Predisposition to Disease
Genome-Wide Association Study
Geographic Mapping
Hospitalization
Host-Pathogen Interactions/genetics
Humans
Inflammation/complications
Information Dissemination
Male
Multifactorial Inheritance
Racial Groups/genetics
SARS-CoV-2/pathogenicity
Smoking

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

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Cite this

Niemi, M. E. K., Karjalainen, J., Liao, R. G., Neale, B. M., Daly, M., Ganna, A., Pathak, G. A., Andrews, S. J., Kanai, M., Veerapen, K., Fernandez-Cadenas, I., Schulte, E. C., Striano, P., Marttila, M., Minica, C., Marouli, E., Karim, M. A., Wendt, F. R., Savage, J., ... COVID-19 Host Genetics Initiative (2021). Mapping the human genetic architecture of COVID-19. Nature, 600(7889), 472-477. https://doi.org/10.1038/s41586-021-03767-x

Niemi, MEK, Karjalainen, J, Liao, RG, Neale, BM, Daly, M, Ganna, A, Pathak, GA, Andrews, SJ, Kanai, M, Veerapen, K, Fernandez-Cadenas, I, Schulte, EC, Striano, P, Marttila, M, Minica, C, Marouli, E, Karim, MA, Wendt, FR, Savage, J, Sloofman, L, Butler-Laporte, G, Kim, HN, Kanoni, S, Okada, Y, Byun, J, Han, Y, Uddin, MJ, Smith, GD, Willer, CJ, Buxbaum, JD, Mehtonen, J, Finucane, H, Cordioli, M, Martin, AR, Zhou, W, Pasaniuc, B, Julienne, H, Aschard, H, Shi, H, Yengo, L, Polimanti, R, Ghoussaini, M, Schwartzentruber, J, Dunham, I, Chwialkowska, K, Francescatto, M, Trankiem, A, Balaconis, MK, Davis, L, Griffin, JL & COVID-19 Host Genetics Initiative 2021, 'Mapping the human genetic architecture of COVID-19', Nature, vol. 600, no. 7889, pp. 472-477. https://doi.org/10.1038/s41586-021-03767-x

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Mapping the human genetic architecture of COVID-19

Abstract

Bibliographical note

Data Availability Statement

Keywords

UN SDGs

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Data from Mapping the human genetic architecture of COVID-19

Cite this

Mapping the human genetic architecture of COVID-19

Abstract

Bibliographical note

Data Availability Statement

Keywords

UN SDGs

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Fingerprint

Datasets

Data from Mapping the human genetic architecture of COVID-19

Cite this