Failure to replicate the association of rare loss-of-function variants in type I IFN immunity genes with severe COVID-19.

Autor: Povysil G; Institute for Genomic Medicine, Columbia University Irving Medical Center, New York, NY, USA., Butler-Laporte G; Lady Davis Institute for Medical Research, Montréal, Québec, Canada.; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montréal, Québec, Canada., Shang N; Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University., Weng C; Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University., Khan A; Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University., Alaamery M; Developmental Medicine Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia.; KACST-BWH Center of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia.; King Abdulaziz City for Science and Technology (KACST)-Saudi Human Genome Satellite Lab at Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia., Nakanishi T; Lady Davis Institute for Medical Research, Montréal, Québec, Canada.; Department of Human Genetics, McGill University, Montréal, Canada.; Kyoto-McGill International Collaborative School in Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.; Research Fellow, Japan Society for the Promotion of Science, Japan., Zhou S; Lady Davis Institute for Medical Research, Montréal, Québec, Canada., Forgetta V; Lady Davis Institute for Medical Research, Montréal, Québec, Canada., Eveleigh R; Canadian Centre for Computational Genomics, McGill University, Montreal, Canada.; McGill Genome Center, McGill University, Montréal, Québec, Canada., Bourgey M; Canadian Centre for Computational Genomics, McGill University, Montreal, Canada.; McGill Genome Center, McGill University, Montréal, Québec, Canada., Aziz N; Canadian COVID Genomics Network, HostSeq Project, Canada., Jones S; Canadian COVID Genomics Network, HostSeq Project, Canada., Knoppers B; Canadian COVID Genomics Network, HostSeq Project, Canada., Scherer S; Canadian COVID Genomics Network, HostSeq Project, Canada., Strug L; Canadian COVID Genomics Network, HostSeq Project, Canada., Lepage P; Canadian Centre for Computational Genomics, McGill University, Montreal, Canada., Ragoussis J; Department of Human Genetics, McGill University, Montréal, Canada.; Canadian Centre for Computational Genomics, McGill University, Montreal, Canada., Bourque G; Department of Human Genetics, McGill University, Montréal, Canada.; McGill Genome Center, McGill University, Montréal, Québec, Canada.; Canadian Centre for Computational Genomics, McGill University, Montreal, Canada., Alghamdi J; Saudi Biobank, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia., Aljawini N; Developmental Medicine Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia.; KACST-BWH Center of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia.; King Abdulaziz City for Science and Technology (KACST)-Saudi Human Genome Satellite Lab at Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia., Albes N; Developmental Medicine Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia.; KACST-BWH Center of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia.; Intensive Care Department, Ministry of National Guard Health Affairs, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Kingdom of Saudi Arabia., Al-Afghani HM; Laboratory Department, Security Forces Hospital, General Directorate of Medical Services, Ministry of Interior, Clinical Laboratory Sciences, Taibah University, Madina, Saudi Arabia., Alghamdi B; Developmental Medicine Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia., Almutair M; Developmental Medicine Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia., Mahmoud ES; King Abdulaziz City for Science and Technology (KACST)-Saudi Human Genome Satellite Lab at Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia., Safie LA; Genomics Research Department, Saudi Human Genome Project, King Fahad Medical City and King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia., Bardisy HE; Genomics Research Department, Saudi Human Genome Project, King Fahad Medical City and King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia., Al Harthi FS; Genomics Research Department, Saudi Human Genome Project, King Fahad Medical City and King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia., Alshareef A; Laboratory Department, Security Forces Hospital, General Directorate of Medical Services, Ministry of Interior, Clinical Laboratory Sciences, Taibah University, Madina, Saudi Arabia., Suliman BA; The Liver Transplant Unit, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia., Alqahtani S; The Liver Transplant Unit, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.; The Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, USA., AlMalik A; Life Science and Environmental Institute, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia., Alrashed MM; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia., Massadeh S; Developmental Medicine Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia.; KACST-BWH Center of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia.; King Abdulaziz City for Science and Technology (KACST)-Saudi Human Genome Satellite Lab at Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia., Mooser V; Department of Human Genetics, McGill University, Montréal, Canada., Lathrop M; Department of Human Genetics, McGill University, Montréal, Canada.; Canadian COVID Genomics Network, HostSeq Project, Canada.; Canadian Centre for Computational Genomics, McGill University, Montreal, Canada., Arabi Y; King Abdulaziz City for Science and Technology (KACST)-Saudi Human Genome Satellite Lab at Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia.; Intensive Care Department, Ministry of National Guard Health Affairs, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Kingdom of Saudi Arabia., Mbarek H; Qatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar Foundation, Doha, Qatar., Saad C; Qatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar Foundation, Doha, Qatar., Al-Muftah W; Qatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar Foundation, Doha, Qatar., Badji R; Qatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar Foundation, Doha, Qatar., Al Thani A; Qatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar Foundation, Doha, Qatar., Ismail SI; Qatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar Foundation, Doha, Qatar., Gharavi AG; Institute for Genomic Medicine, Columbia University Irving Medical Center, New York, NY, USA.; Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University.; Center for Precision Medicine and Genomics. Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York, USA., Abedalthagafi MS; Genomics Research Department, Saudi Human Genome Project, King Fahad Medical City and King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.; Life Science and Environmental Institute, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia., Richards JB; Lady Davis Institute for Medical Research, Montréal, Québec, Canada.; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montréal, Québec, Canada.; Department of Human Genetics, McGill University, Montréal, Canada.; Department of Twin Research, King's College London, London, UK., Goldstein DB; Institute for Genomic Medicine, Columbia University Irving Medical Center, New York, NY, USA.; Department of Genetics & Development, Columbia University, New York, New York, USA., Kiryluk K; Institute for Genomic Medicine, Columbia University Irving Medical Center, New York, NY, USA.; Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University.
Jazyk: angličtina
Zdroj: MedRxiv : the preprint server for health sciences [medRxiv] 2020 Dec 21. Date of Electronic Publication: 2020 Dec 21.
DOI: 10.1101/2020.12.18.20248226
Abstrakt: 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 1,934 COVID-19 cases (713 with severe and 1,221 with mild disease) and 15,251 ancestry-matched population controls across four independent COVID-19 biobanks. We then tested if rare pLOF variants in these 13 genes were associated with severe COVID-19. We identified only one rare pLOF mutation across these genes amongst 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 find no evidence of association of rare loss-of-function variants in the proposed 13 candidate genes with severe COVID-19 outcomes.
Databáze: MEDLINE