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; S Lee; J Priest; A Renieri; VG Sankaran; Heel D van; P Deelen; JB Richards; T Nakanishi; L Biesecker; VE Kerchberger; JK Baillie; F Mari; A Bernasconi; SC Baillie; A Canakoglu; B Wolford; A Faucon; AK Dutta; C Schurmann; E Harry; E Birney; H Nguyen; J Nasir; M Kaunisto; M Solomonson; N Dueker; N Vadgama; S Limou; S Rahmouni; H Mbarek; D Darwish; Mohammed Jashim Uddin; R Albertos; J Pérez-Tur; R Li; L Folkersen; I Moltke; N Koelling; A Teumer; Kousath

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^*, 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 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, S Lee, J Priest, A Renieri, VG Sankaran, Heel D van, P Deelen, JB Richards, T Nakanishi, L Biesecker, VE Kerchberger, JK Baillie, F Mari, A Bernasconi, SC Baillie, A Canakoglu, B Wolford, A Faucon, AK Dutta, C Schurmann, E Harry, E Birney, H Nguyen, J Nasir, M Kaunisto, M Solomonson, N Dueker, N Vadgama, S Limou, S Rahmouni, H Mbarek, D Darwish, Mohammed Jashim Uddin, R Albertos, J Pérez-Tur, R Li, L Folkersen, I Moltke, N Koelling, A Teumer, Kousath

^*Corresponding author for this work

Peninsula Medical School

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

Abstract

AbstractThe 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.

Original language	English
Pages (from-to)	472-477
Number of pages	0
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 - 16 Dec 2021

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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., ... Kousath (2021). Mapping the human genetic architecture of COVID-19. Nature, 600(7889), 472-477. https://doi.org/10.1038/s41586-021-03767-x

@article{5c0451e68deb4c73b02e5038a2f0fe1e,

title = "Mapping the human genetic architecture of COVID-19",

abstract = "AbstractThe 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.",

author = "Niemi, \{Mari E.K.\} and Juha Karjalainen and Liao, \{Rachel G.\} and Neale, \{Benjamin M.\} and Mark Daly and Andrea Ganna and Pathak, \{Gita A.\} and Andrews, \{Shea J.\} and Masahiro Kanai and Kumar Veerapen and Israel Fernandez-Cadenas and Schulte, \{Eva C.\} and Pasquale Striano and Minttu Marttila and Camelia Minica and Eirini Marouli and Karim, \{Mohd Anisul\} and Wendt, \{Frank R.\} and Jeanne Savage and Laura Sloofman and Guillaume Butler-Laporte and Kim, \{Han Na\} and Stavroula Kanoni and Yukinori Okada and Jinyoung Byun and Younghun Han and Uddin, \{Mohammed Jashim\} and Smith, \{George Davey\} and Willer, \{Cristen J.\} and Buxbaum, \{Joseph D.\} and Juha Mehtonen and Hilary Finucane and Mattia Cordioli and Martin, \{Alicia R.\} and Wei Zhou and Bogdan Pasaniuc and Hanna Julienne and Hugues Aschard and Huwenbo Shi and Loic Yengo and Renato Polimanti and Maya Ghoussaini and Jeremy Schwartzentruber and Ian Dunham and Karolina Chwialkowska and Margherita Francescatto and Amy Trankiem and Balaconis, \{Mary K.\} and Lea Davis and S Lee and J Priest and A Renieri and VG Sankaran and van, \{Heel D\} and P Deelen and JB Richards and T Nakanishi and L Biesecker and VE Kerchberger and JK Baillie and F Mari and A Bernasconi and SC Baillie and A Canakoglu and B Wolford and A Faucon and AK Dutta and C Schurmann and E Harry and E Birney and H Nguyen and J Nasir and M Kaunisto and M Solomonson and N Dueker and N Vadgama and S Limou and S Rahmouni and H Mbarek and D Darwish and Uddin, \{Mohammed Jashim\} and R Albertos and J P{\'e}rez-Tur and R Li and L Folkersen and I Moltke and N Koelling and A Teumer and Kousath",

year = "2021",

month = dec,

day = "16",

doi = "10.1038/s41586-021-03767-x",

language = "English",

volume = "600",

pages = "472--477",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "7889",

}

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, Lee, S, Priest, J, Renieri, A, Sankaran, VG, van, HD, Deelen, P, Richards, JB, Nakanishi, T, Biesecker, L, Kerchberger, VE, Baillie, JK, Mari, F, Bernasconi, A, Baillie, SC, Canakoglu, A, Wolford, B, Faucon, A, Dutta, AK, Schurmann, C, Harry, E, Birney, E, Nguyen, H, Nasir, J, Kaunisto, M, Solomonson, M, Dueker, N, Vadgama, N, Limou, S, Rahmouni, S, Mbarek, H, Darwish, D, Uddin, MJ, Albertos, R, Pérez-Tur, J, Li, R, Folkersen, L, Moltke, I, Koelling, N, Teumer, A & Kousath 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

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 - 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 - Lee, S

AU - Priest, J

AU - Renieri, A

AU - Sankaran, VG

AU - van, Heel D

AU - Deelen, P

AU - Richards, JB

AU - Nakanishi, T

AU - Biesecker, L

AU - Kerchberger, VE

AU - Baillie, JK

AU - Mari, F

AU - Bernasconi, A

AU - Baillie, SC

AU - Canakoglu, A

AU - Wolford, B

AU - Faucon, A

AU - Dutta, AK

AU - Schurmann, C

AU - Harry, E

AU - Birney, E

AU - Nguyen, H

AU - Nasir, J

AU - Kaunisto, M

AU - Solomonson, M

AU - Dueker, N

AU - Vadgama, N

AU - Limou, S

AU - Rahmouni, S

AU - Mbarek, H

AU - Darwish, D

AU - Uddin, Mohammed Jashim

AU - Albertos, R

AU - Pérez-Tur, J

AU - Li, R

AU - Folkersen, L

AU - Moltke, I

AU - Koelling, N

AU - Teumer, A

AU - Kousath, null

PY - 2021/12/16

Y1 - 2021/12/16

N2 - AbstractThe 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 - AbstractThe 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.

U2 - 10.1038/s41586-021-03767-x

DO - 10.1038/s41586-021-03767-x

M3 - Article

SN - 0028-0836

VL - 600

SP - 472

EP - 477

JO - Nature

JF - Nature

IS - 7889

ER -

Mapping the human genetic architecture of COVID-19

Abstract

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