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

Journal: The Journal Of Clinical Investigation

Published: January 19, 2021

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.

Authors

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

Relevant Conditions

Severe Acute Respiratory Syndrome (SARS), COVID-19

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

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