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

A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF-7 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 wi...

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Bibliographic Details
Published in:The Journal of clinical investigation Vol. 131; no. 14
Main Authors: Povysil, Gundula, Butler-Laporte, Guillaume, Shang, Ning, Wang, Chen, Khan, Atlas, Alaamery, Manal, Nakanishi, Tomoko, Zhou, Sirui, Forgetta, Vincenzo, Eveleigh, Robert J.M., Bourgey, Mathieu, Aziz, Naveed, Jones, Steven J.M., Knoppers, Bartha, Scherer, Stephen W., Strug, Lisa J., Lepage, Pierre, Ragoussis, Jiannis, Bourque, Guillaume, Alghamdi, Jahad, Aljawini, Nora, Albes, Nour, Al-Afghani, Hani M., Alghamdi, Bader, Almutairi, Mansour S., Mahmoud, Ebrahim Sabri, Abu-Safieh, Leen, El Bardisy, Hadeel, Harthi, Fawz S. Al, Alshareef, Abdulraheem, Suliman, Bandar Ali, Alqahtani, Saleh A., Almalik, Abdulaziz, Alrashed, May M., Massadeh, Salam, Mooser, Vincent, Lathrop, Mark, Fawzy, Mohamed, Arabi, Yaseen M., Mbarek, Hamdi, Saad, Chadi, Al-Muftah, Wadha, Jung, Junghyun, Mangul, Serghei, Badji, Radja, Thani, Asma Al, Ismail, Said I., Gharavi, Ali G., Abedalthagafi, Malak S., Richards, J. Brent, Goldstein, David B., Kiryluk, Krzysztof
Format: Journal Article
Language:English
Published: American Society for Clinical Investigation 15.07.2021
Subjects:
Concise Communication
Genetic aspects
Genetic research
Genetic variation
Health aspects
Interferon
United States
ISSN:1558-8238, 0021-9738, 1558-8238
Online Access:Get full text
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Summary:A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF-7 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.
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ISSN:1558-8238
0021-9738
1558-8238
DOI:10.1172/JCI147834