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


Journal

medRxiv : the preprint server for health sciences
Titre abrégé: medRxiv
Pays: United States
ID NLM: 101767986

Informations de publication

Date de publication:
21 Dec 2020
Historique:
pubmed: 6 1 2021
medline: 6 1 2021
entrez: 5 1 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 33398295
doi: 10.1101/2020.12.18.20248226
pmc: PMC7781338
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : NIA NIH HHS
ID : RF1 AG054023
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001873
Pays : United States

Commentaires et corrections

Type : UpdateIn

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Auteurs

Gundula Povysil (G)

Institute for Genomic Medicine, Columbia University Irving Medical Center, New York, NY, USA.

Guillaume Butler-Laporte (G)

Lady Davis Institute for Medical Research, Montréal, Québec, Canada.
Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montréal, Québec, Canada.

Ning Shang (N)

Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University.

Chen Weng (C)

Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University.

Atlas Khan (A)

Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University.

Manal 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.

Tomoko 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.

Sirui Zhou (S)

Lady Davis Institute for Medical Research, Montréal, Québec, Canada.

Vincenzo Forgetta (V)

Lady Davis Institute for Medical Research, Montréal, Québec, Canada.

Robert Eveleigh (R)

Canadian Centre for Computational Genomics, McGill University, Montreal, Canada.
McGill Genome Center, McGill University, Montréal, Québec, Canada.

Mathieu Bourgey (M)

Canadian Centre for Computational Genomics, McGill University, Montreal, Canada.
McGill Genome Center, McGill University, Montréal, Québec, Canada.

Naveed Aziz (N)

Canadian COVID Genomics Network, HostSeq Project, Canada.

Steven Jones (S)

Canadian COVID Genomics Network, HostSeq Project, Canada.

Bartha Knoppers (B)

Canadian COVID Genomics Network, HostSeq Project, Canada.

Stephen Scherer (S)

Canadian COVID Genomics Network, HostSeq Project, Canada.

Lisa Strug (L)

Canadian COVID Genomics Network, HostSeq Project, Canada.

Pierre Lepage (P)

Canadian Centre for Computational Genomics, McGill University, Montreal, Canada.

Jiannis Ragoussis (J)

Department of Human Genetics, McGill University, Montréal, Canada.
Canadian Centre for Computational Genomics, McGill University, Montreal, Canada.

Guillaume 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.

Jahad 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.

Nora 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.

Nour 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.

Hani M Al-Afghani (HM)

Laboratory Department, Security Forces Hospital, General Directorate of Medical Services, Ministry of Interior, Clinical Laboratory Sciences, Taibah University, Madina, Saudi Arabia.

Bader 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.

Mansour 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.

Ebrahim Sabri 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.

Leen Abu Safie (LA)

Genomics Research Department, Saudi Human Genome Project, King Fahad Medical City and King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.

Hadeel El Bardisy (HE)

Genomics Research Department, Saudi Human Genome Project, King Fahad Medical City and King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.

Fawz S 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.

Abdulraheem Alshareef (A)

Laboratory Department, Security Forces Hospital, General Directorate of Medical Services, Ministry of Interior, Clinical Laboratory Sciences, Taibah University, Madina, Saudi Arabia.

Bandar Ali Suliman (BA)

The Liver Transplant Unit, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

Saleh 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.

Abdulaziz AlMalik (A)

Life Science and Environmental Institute, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.

May M Alrashed (MM)

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.

Salam 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.

Vincent Mooser (V)

Department of Human Genetics, McGill University, Montréal, Canada.

Mark 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.

Yaseen 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.

Hamdi Mbarek (H)

Qatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar Foundation, Doha, Qatar.

Chadi Saad (C)

Qatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar Foundation, Doha, Qatar.

Wadha Al-Muftah (W)

Qatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar Foundation, Doha, Qatar.

Radja Badji (R)

Qatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar Foundation, Doha, Qatar.

Asma Al Thani (A)

Qatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar Foundation, Doha, Qatar.

Said I Ismail (SI)

Qatar Genome Program, Qatar Foundation Research, Development and Innovation, Qatar Foundation, Doha, Qatar.

Ali G 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.

Malak S 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.

J Brent 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.

David B 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.

Krzysztof 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.

Classifications MeSH