Failure to replicate the association of rare loss-of-function variants in type I IFN immunity genes with severe COVID-19
Failure to replicate the association of rare loss-of-function variants in type I IFN immunity genes 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 1,934 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.
Aljawini Nora、Mooser Vincent、Alghamdi Bader、Alshareef Abdulraheem、Arabi Yaseen、Weng Chen、Alaamery Manal、Forgetta Vincenzo、Eveleigh Robert、Scherer Stephen、Al-Afghani Hani M.、Almutair Mansour、Safie Leen Abu、AlMalik Abdulaziz、Massadeh Salam、Mbarek Hamdi、Al-Muftah Wadha、Ismail Said I.、Gharavi Ali G.、Khan Atlas、Bourque Guillaume、Suliman Bandar Ali、Saad Chadi、Richards J Brent、Mahmoud Ebrahim Sabri、Thani Asma Al、Kiryluk Krzysztof、Nakanishi Tomoko、Ragoussis Jiannis、Albes Nour、Alghamdi Jahad、Alqahtani Saleh、Aziz Naveed、Shang Ning、Jones Steven、Lathrop Mark、Abedalthagafi Malak S.、Lepage Pierre、Zhou Sirui、Povysil Gundula、Strug Lisa、Harthi Fawz S. Al、Butler-Laporte Guillaume、Badji Radja、Bourgey Mathieu、Knoppers Bartha、Bardisy Hadeel El、Goldstein David B.、Alrashed May 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)||KACST-BWH Center of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology (KACST)||King Abdulaziz City for Science and Technology (KACST)-Saudi Human Genome Satellite Lab at Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA)Department of Human Genetics, McGill UniversityDevelopmental 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)Laboratory Department, Security Forces Hospital, General Directorate of Medical Services, Ministry of Interior, Clinical Laboratory Sciences, Taibah UniversityKing Abdulaziz City for Science and Technology (KACST)-Saudi Human Genome Satellite Lab at Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA)||Intensive Care Department, Ministry of National Guard Health Affairs, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research CenterDivision of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia UniversityDevelopmental 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)||KACST-BWH Center of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology (KACST)||King Abdulaziz City for Science and Technology (KACST)-Saudi Human Genome Satellite Lab at Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA)Lady Davis Institute for Medical Research, Montr¨|alCanadian Centre for Computational Genomics, McGill University||McGill Genome Center, McGill University, Montr¨|alCanadian COVID Genomics Network, HostSeq ProjectLaboratory Department, Security Forces Hospital, General Directorate of Medical Services, Ministry of Interior, Clinical Laboratory Sciences, Taibah UniversityDevelopmental 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)Genomics Research Department, Saudi Human Genome Project, King Fahad Medical City and King Abdulaziz City for Science and TechnologyLife Science and Environmental Institute, King Abdulaziz City for Science and TechnologyDevelopmental 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)||KACST-BWH Center of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology (KACST)||King Abdulaziz City for Science and Technology (KACST)-Saudi Human Genome Satellite Lab at Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA)Qatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar FoundationQatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar FoundationQatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar FoundationInstitute for Genomic Medicine, Columbia University Irving Medical Center||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 UniversityDivision of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia UniversityDepartment of Human Genetics, McGill University||McGill Genome Center, McGill University, Montr¨|al||Canadian Centre for Computational Genomics, McGill UniversityThe Liver Transplant Unit, King Faisal Specialist Hospital and Research CentreQatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar FoundationLady Davis Institute for Medical Research, Montr¨|al||Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montr¨|al||Department of Human Genetics, McGill University||Department of Twin Research, King?ˉs College LondonKing Abdulaziz City for Science and Technology (KACST)-Saudi Human Genome Satellite Lab at Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA)Qatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar FoundationInstitute for Genomic Medicine, Columbia University Irving Medical Center||Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia UniversityLady Davis Institute for Medical Research, Montr¨|al||Department of Human Genetics, McGill University||Kyoto-McGill International Collaborative School in Genomic Medicine, Graduate School of Medicine, Kyoto University||Research Fellow, Japan Society for the Promotion of ScienceDepartment of Human Genetics, McGill University||Canadian Centre for Computational Genomics, McGill UniversityDevelopmental 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)||KACST-BWH Center of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology (KACST)||Intensive Care Department, Ministry of National Guard Health Affairs, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research CenterSaudi Biobank, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health AffairsThe Liver Transplant Unit, King Faisal Specialist Hospital and Research Centre||The Division of Gastroenterology and Hepatology, Johns Hopkins UniversityCanadian COVID Genomics Network, HostSeq ProjectDivision of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia UniversityCanadian COVID Genomics Network, HostSeq ProjectDepartment of Human Genetics, McGill University||Canadian COVID Genomics Network, HostSeq Project||Canadian Centre for Computational Genomics, McGill UniversityGenomics Research Department, Saudi Human Genome Project, King Fahad Medical City and King Abdulaziz City for Science and Technology||Life Science and Environmental Institute, King Abdulaziz City for Science and TechnologyCanadian Centre for Computational Genomics, McGill UniversityLady Davis Institute for Medical Research, Montr¨|alInstitute for Genomic Medicine, Columbia University Irving Medical CenterCanadian COVID Genomics Network, HostSeq ProjectGenomics Research Department, Saudi Human Genome Project, King Fahad Medical City and King Abdulaziz City for Science and TechnologyLady Davis Institute for Medical Research, Montr¨|al||Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montr¨|alQatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar FoundationCanadian Centre for Computational Genomics, McGill University||McGill Genome Center, McGill University, Montr¨|alCanadian COVID Genomics Network, HostSeq ProjectGenomics Research Department, Saudi Human Genome Project, King Fahad Medical City and King Abdulaziz City for Science and TechnologyInstitute for Genomic Medicine, Columbia University Irving Medical Center||Department of Genetics & Development, Columbia UniversityDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University
医学研究方法基础医学生物科学研究方法、生物科学研究技术
Aljawini Nora,Mooser Vincent,Alghamdi Bader,Alshareef Abdulraheem,Arabi Yaseen,Weng Chen,Alaamery Manal,Forgetta Vincenzo,Eveleigh Robert,Scherer Stephen,Al-Afghani Hani M.,Almutair Mansour,Safie Leen Abu,AlMalik Abdulaziz,Massadeh Salam,Mbarek Hamdi,Al-Muftah Wadha,Ismail Said I.,Gharavi Ali G.,Khan Atlas,Bourque Guillaume,Suliman Bandar Ali,Saad Chadi,Richards J Brent,Mahmoud Ebrahim Sabri,Thani Asma Al,Kiryluk Krzysztof,Nakanishi Tomoko,Ragoussis Jiannis,Albes Nour,Alghamdi Jahad,Alqahtani Saleh,Aziz Naveed,Shang Ning,Jones Steven,Lathrop Mark,Abedalthagafi Malak S.,Lepage Pierre,Zhou Sirui,Povysil Gundula,Strug Lisa,Harthi Fawz S. Al,Butler-Laporte Guillaume,Badji Radja,Bourgey Mathieu,Knoppers Bartha,Bardisy Hadeel El,Goldstein David B.,Alrashed May M..Failure to replicate the association of rare loss-of-function variants in type I IFN immunity genes with severe COVID-19[EB/OL].(2025-03-28)[2025-08-03].https://www.medrxiv.org/content/10.1101/2020.12.18.20248226.点此复制
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