@article{09323827550e4c1986529bb0ca9be841,
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 = "Funding Information: We would like to thank all study participants for contributing to the biobanks used in this study. Sequencing and phenotyping of the Columbia cohort was made possible by the Columbia COVID-19 Genomics Workgroup, including Andrea Califano, Wendy Chung, Christine K. Garcia, Iuliana Ionita-Laza, Richard Mayeux, Sheila M. O{\textquoteright}Byrne, Danielle Pendrick, Muredach P. Reilly, Soumitra Sengupta, Peter Sims, and Anne-Catrin Uhlemann. We thank the Saudi genome members and collaborators including Sameera Al-Johani, Majid Alfadhel, Deema Zahrani, Moneera Alsuwailem, Nouf AlDhawi, Eman Barhoush, Batoul Baz, Faris AlKhlifi, Sarah AlKwai, Maha Albeladi, Faisal Almalki, Iman Mohammad, Ahmed Alaskar, Ebtehal A. Alsolm, Sara S. Alotaibi, Aljohara A. Albabtain, Dona Baraka, Rana Hasanato, Hamza A. Alghamdi, Laila S. Al-Awdah, Amin K. Khattab, Roaa Talal Halawani, Ziab Zakey Alahmadey, Jehad Khalid Albakri, and Walaa Ali Felemban. The authors would like to acknowledge the King Abdullah International Medical Research Center (KAIMRC) for their continuous support. In addition, we thank all the developmental medicine department members for their contributions. We acknowledge King Abdulaziz City for Science and Technology (KACST) for their support through the Saudi Human Genome Project (SHGP) and the Therapy Development Research Program (TDRP). We also thank the Qatar Biobank for data collection and phenotyping. The Qatar Genome Program and Biobank are both Research, Development & Innovation entities within Qatar Foundation for Education, Science and Community Development. We are also thankful to Laith Abu Raddad for EMR data extraction. The Columbia COVID-19 Biobank is supported by the Vagelos College of Physicians & Surgeons Office for Research, Precision Medicine Resource, and Biomedical Informatics Resource of the Columbia University Irving Institute for Clinical and Translational Research (CTSA). Columbia CTSA is funded by the National Center for Advancing Translational Sciences (UL1TR001873). A portion of population controls were from the Washington Heights–Inwood Columbia Aging Project (AG054023). Genome sequencing of Biobanque Qu{\'e}bec COVID-19 was funded by the CanCOGeN HostSeq project, with contribution from Fonds de Recherche Qu{\'e}-bec Sant{\'e} (FRQS), G{\'e}nome Qu{\'e}bec, and the Public Health Agency of Canada. The Richards group is supported by the Canadian Institutes of Health Research (CIHR), the Lady Davis Institute of the Jewish General Hospital, the Canadian Foundation for Innovation, the NIH, Cancer Research UK, and FRQS. MA and MS Abedalthagafi acknowledge King Abdulaziz City for Science and Technology and the Saudi Human Genome Project for technical and financial support. MMR was supported by Research Support- ing Project number (RSP-2020/1), King Saud University, Riyadh, Saudi Arabia. GBL is supported by a joint research fellowship from Quebec{\textquoteright}s Ministry of Health and Social Services, and the FRQS. TN is supported by Research Fellowships of Japan Society for the Promotion of Science (JSPS) for Young Scientists and JSPS Overseas Challenge Program for Young Researchers. JBR is supported by a FRQS Clinical Research Scholarship. This study is part of the www.covid19hg.org consortium. Publisher Copyright: {\textcopyright} 2021, American Society for Clinical Investigation.",
year = "2021",
month = jul,
doi = "10.1172/JCI147834",
language = "English (US)",
volume = "131",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "14",
}