Rare loss-of-function variants in type I IFN immunity genes are not associated with severe COVID-19

Gundula Povysil; Guillaume Butler-Laporte; Ning Shang; Chen Wang; Atlas Khan; Manal Alaamery; Tomoko Nakanishi; Sirui Zhou; Vincenzo Forgetta; Robert J.M. Eveleigh; Mathieu Bourgey; Naveed Aziz; Steven J.M. Jones; Bartha Knoppers; Stephen W. Scherer; Lisa J. Strug; Pierre Lepage; Jiannis Ragoussis; Guillaume Bourque; Jahad Alghamdi; Nora Aljawini; Nour Albes; Hani M. Al-Afghani; Bader Alghamdi; Mansour S. Almutairi; Ebrahim Sabri Mahmoud; Leen Abu-Safieh; Hadeel El Bardisy; Fawz S. Al Harthi; Abdulraheem Alshareef; Bandar Ali Suliman; Saleh A. Alqahtani; Abdulaziz Almalik; May M. Alrashed; Salam Massadeh; Vincent Mooser; Mark Lathrop; Mohamed Fawzy; Yaseen M. Arabi; Hamdi Mbarek; Chadi Saad; Wadha Al-Muftah; Junghyun Jung; Serghei Mangul; Radja Badji; Asma Al Thani; Said I. Ismail; Ali G. Gharavi; Malak S. Abedalthagafi; J. Brent Richards; David B. Goldstein; Krzysztof Kiryluk

doi:10.1172/JCI147834

Rare loss-of-function variants in type I IFN immunity genes are not associated with severe COVID-19

Gundula Povysil
, Guillaume Butler-Laporte
, Ning Shang
, Chen Wang
, Atlas Khan
, Manal Alaamery
, Tomoko Nakanishi
, Sirui Zhou
, Vincenzo Forgetta
, Robert J.M. Eveleigh
, Mathieu Bourgey
, Naveed Aziz
, Steven J.M. Jones
, Bartha Knoppers
, Stephen W. Scherer
, Lisa J. Strug
, Pierre Lepage
, Jiannis Ragoussis
, Guillaume Bourque
, Jahad Alghamdi

Nora Aljawini, Nour Albes, Hani M. Al-Afghani, Bader Alghamdi, Mansour S. Almutairi, Ebrahim Sabri Mahmoud, Leen Abu-Safieh, Hadeel El Bardisy, Fawz S. Al Harthi, Abdulraheem Alshareef, Bandar Ali Suliman, Saleh A. Alqahtani, Abdulaziz Almalik, May M. Alrashed, Salam Massadeh, Vincent Mooser, Mark Lathrop, Mohamed Fawzy, Yaseen M. Arabi, Hamdi Mbarek, Chadi Saad, Wadha Al-Muftah, Junghyun Jung, Serghei Mangul, Radja Badji, Asma Al Thani, Said I. Ismail, Ali G. Gharavi, Malak S. Abedalthagafi, J. Brent Richards^*, David B. Goldstein^*, Krzysztof Kiryluk^*

^*Corresponding author for this work

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

Abstract

A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF7-dependent type I IFN pathways explain up to 3.5% of severe COVID-19 cases. We performed whole-exome or whole-genome sequencing of 1,864 COVID-19 cases (713 with severe and 1,151 with mild disease) and 15,033 ancestry-matched population controls across 4 independent COVID-19 biobanks. We tested whether rare pLOF variants in these 13 genes were associated with severe COVID-19. We identified only 1 rare pLOF mutation across these genes among 713 cases with severe COVID-19 and observed no enrichment of pLOFs in severe cases compared to population controls or mild COVID-19 cases. We found no evidence of association of rare LOF variants in the 13 candidate genes with severe COVID-19 outcomes.

Original language	English
Article number	e147834
Journal	Journal of Clinical Investigation
Volume	131
Issue number	14
DOIs	https://doi.org/10.1172/JCI147834
Publication status	Published - Jul 2021
Externally published	Yes

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Povysil, G., Butler-Laporte, G., Shang, N., Wang, C., Khan, A., Alaamery, M., Nakanishi, T., Zhou, S., Forgetta, V., Eveleigh, R. J. M., Bourgey, M., Aziz, N., Jones, S. J. M., Knoppers, B., Scherer, S. W., Strug, L. J., Lepage, P., Ragoussis, J., Bourque, G., ... Kiryluk, K. (2021). Rare loss-of-function variants in type I IFN immunity genes are not associated with severe COVID-19. Journal of Clinical Investigation, 131(14), Article e147834. https://doi.org/10.1172/JCI147834

@article{9ce6ba0277d2440a8c9fed2003c36cc7,

title = "Rare loss-of-function variants in type I IFN immunity genes are not associated with severe COVID-19",

abstract = "A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF7-dependent type I IFN pathways explain up to 3.5\% of severe COVID-19 cases. We performed whole-exome or whole-genome sequencing of 1,864 COVID-19 cases (713 with severe and 1,151 with mild disease) and 15,033 ancestry-matched population controls across 4 independent COVID-19 biobanks. We tested whether rare pLOF variants in these 13 genes were associated with severe COVID-19. We identified only 1 rare pLOF mutation across these genes among 713 cases with severe COVID-19 and observed no enrichment of pLOFs in severe cases compared to population controls or mild COVID-19 cases. We found no evidence of association of rare LOF variants in the 13 candidate genes with severe COVID-19 outcomes.",

author = "Gundula Povysil and Guillaume Butler-Laporte and Ning Shang and Chen Wang and Atlas Khan and Manal Alaamery and Tomoko Nakanishi and Sirui Zhou and Vincenzo Forgetta and Eveleigh, \{Robert J.M.\} and Mathieu Bourgey and Naveed Aziz and Jones, \{Steven J.M.\} and Bartha Knoppers and Scherer, \{Stephen W.\} and Strug, \{Lisa J.\} and Pierre Lepage and Jiannis Ragoussis and Guillaume Bourque and Jahad Alghamdi and Nora Aljawini and Nour Albes and Al-Afghani, \{Hani M.\} and Bader Alghamdi and Almutairi, \{Mansour S.\} and Mahmoud, \{Ebrahim Sabri\} and Leen Abu-Safieh and \{El Bardisy\}, Hadeel and \{Al Harthi\}, \{Fawz S.\} and Abdulraheem Alshareef and Suliman, \{Bandar Ali\} and Alqahtani, \{Saleh A.\} and Abdulaziz Almalik and Alrashed, \{May M.\} and Salam Massadeh and Vincent Mooser and Mark Lathrop and Mohamed Fawzy and Arabi, \{Yaseen M.\} and Hamdi Mbarek and Chadi Saad and Wadha Al-Muftah and Junghyun Jung and Serghei Mangul and Radja Badji and Thani, \{Asma Al\} and Ismail, \{Said I.\} and Gharavi, \{Ali G.\} and Abedalthagafi, \{Malak S.\} and Richards, \{J. Brent\} and Goldstein, \{David B.\} and Krzysztof Kiryluk",

note = "Publisher Copyright: {\textcopyright} 2021, American Society for Clinical Investigation.",

year = "2021",

month = jul,

doi = "10.1172/JCI147834",

language = "English",

volume = "131",

journal = "Journal of Clinical Investigation",

issn = "0021-9738",

publisher = "American Society for Clinical Investigation",

number = "14",

}

Povysil, G, Butler-Laporte, G, Shang, N, Wang, C, Khan, A, Alaamery, M, Nakanishi, T, Zhou, S, Forgetta, V, Eveleigh, RJM, Bourgey, M, Aziz, N, Jones, SJM, Knoppers, B, Scherer, SW, Strug, LJ, Lepage, P, Ragoussis, J, Bourque, G, Alghamdi, J, Aljawini, N, Albes, N, Al-Afghani, HM, Alghamdi, B, Almutairi, MS, Mahmoud, ES, Abu-Safieh, L, El Bardisy, H, Al Harthi, FS, Alshareef, A, Suliman, BA, Alqahtani, SA, Almalik, A, Alrashed, MM, Massadeh, S, Mooser, V, Lathrop, M, Fawzy, M, Arabi, YM, Mbarek, H, Saad, C, Al-Muftah, W, Jung, J, Mangul, S, Badji, R, Thani, AA, Ismail, SI, Gharavi, AG, Abedalthagafi, MS, Richards, JB, Goldstein, DB & Kiryluk, K 2021, 'Rare loss-of-function variants in type I IFN immunity genes are not associated with severe COVID-19', Journal of Clinical Investigation, vol. 131, no. 14, e147834. https://doi.org/10.1172/JCI147834

TY - JOUR

T1 - Rare loss-of-function variants in type I IFN immunity genes are not associated with severe COVID-19

AU - Povysil, Gundula

AU - Butler-Laporte, Guillaume

AU - Shang, Ning

AU - Wang, Chen

AU - Khan, Atlas

AU - Alaamery, Manal

AU - Nakanishi, Tomoko

AU - Zhou, Sirui

AU - Forgetta, Vincenzo

AU - Eveleigh, Robert J.M.

AU - Bourgey, Mathieu

AU - Aziz, Naveed

AU - Jones, Steven J.M.

AU - Knoppers, Bartha

AU - Scherer, Stephen W.

AU - Strug, Lisa J.

AU - Lepage, Pierre

AU - Ragoussis, Jiannis

AU - Bourque, Guillaume

AU - Alghamdi, Jahad

AU - Aljawini, Nora

AU - Albes, Nour

AU - Al-Afghani, Hani M.

AU - Alghamdi, Bader

AU - Almutairi, Mansour S.

AU - Mahmoud, Ebrahim Sabri

AU - Abu-Safieh, Leen

AU - El Bardisy, Hadeel

AU - Al Harthi, Fawz S.

AU - Alshareef, Abdulraheem

AU - Suliman, Bandar Ali

AU - Alqahtani, Saleh A.

AU - Almalik, Abdulaziz

AU - Alrashed, May M.

AU - Massadeh, Salam

AU - Mooser, Vincent

AU - Lathrop, Mark

AU - Fawzy, Mohamed

AU - Arabi, Yaseen M.

AU - Mbarek, Hamdi

AU - Saad, Chadi

AU - Al-Muftah, Wadha

AU - Jung, Junghyun

AU - Mangul, Serghei

AU - Badji, Radja

AU - Thani, Asma Al

AU - Ismail, Said I.

AU - Gharavi, Ali G.

AU - Abedalthagafi, Malak S.

AU - Richards, J. Brent

AU - Goldstein, David B.

AU - Kiryluk, Krzysztof

PY - 2021/7

Y1 - 2021/7

N2 - A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF7-dependent type I IFN pathways explain up to 3.5% of severe COVID-19 cases. We performed whole-exome or whole-genome sequencing of 1,864 COVID-19 cases (713 with severe and 1,151 with mild disease) and 15,033 ancestry-matched population controls across 4 independent COVID-19 biobanks. We tested whether rare pLOF variants in these 13 genes were associated with severe COVID-19. We identified only 1 rare pLOF mutation across these genes among 713 cases with severe COVID-19 and observed no enrichment of pLOFs in severe cases compared to population controls or mild COVID-19 cases. We found no evidence of association of rare LOF variants in the 13 candidate genes with severe COVID-19 outcomes.

AB - A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF7-dependent type I IFN pathways explain up to 3.5% of severe COVID-19 cases. We performed whole-exome or whole-genome sequencing of 1,864 COVID-19 cases (713 with severe and 1,151 with mild disease) and 15,033 ancestry-matched population controls across 4 independent COVID-19 biobanks. We tested whether rare pLOF variants in these 13 genes were associated with severe COVID-19. We identified only 1 rare pLOF mutation across these genes among 713 cases with severe COVID-19 and observed no enrichment of pLOFs in severe cases compared to population controls or mild COVID-19 cases. We found no evidence of association of rare LOF variants in the 13 candidate genes with severe COVID-19 outcomes.

UR - https://www.scopus.com/pages/publications/85107768941

U2 - 10.1172/JCI147834

DO - 10.1172/JCI147834

M3 - Article

C2 - 34043590

AN - SCOPUS:85107768941

SN - 0021-9738

VL - 131

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

IS - 14

M1 - e147834

ER -

Rare loss-of-function variants in type I IFN immunity genes are not associated with severe COVID-19

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