Scopus
🔓 Açık Erişim YÖKSİS Eşleşti
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
Genome Medicine · Aralık 2023
YÖKSİS Kayıtları
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
Genome Medicine · 2023 SCI-Expanded
DOÇENT GÜLSÜM ALKAN →
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
Genome Medicine · 2023 SCI-Expanded
PROFESÖR JALE BENGİ ÇELİK →
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
Genome Medicine · 2023 SCI-Expanded
DOÇENT MELİKE EMİROĞLU →
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
Genome Medicine · 2023 SCI-Expanded
DOÇENT GÜLSÜM ALKAN →
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.
Genome medicine · 2023 SCI-Expanded
DOÇENT GÜLSÜM ALKAN →
Makale Bilgileri
DergiGenome Medicine
Yayın TarihiAralık 2023
Cilt / Sayfa15
Scopus ID2-s2.0-85160044322
Erişim🔓 Açık Erişim
Özet
Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
Yazarlar (100)
1
Daniela Matuozzo
2
Estelle Talouarn
ORCID: 0000-0002-5016-0446
3
Astrid Marchal
4
Peng Zhang
5
Jeremy Manry
6
Yoann Seeleuthner
ORCID: 0000-0002-1878-8567
7
Yu Zhang
8
Alexandre Bolze
ORCID: 0000-0001-7399-2766
9
Matthieu Chaldebas
10
Baptiste Milisavljevic
11
Adrian Gervais
12
Paul Bastard
13
Takaki Asano
14
Lucy Bizien
15
Federica Barzaghi
16
Hassan Abolhassani
17
Ahmad Abou Tayoun
18
Alessandro Aiuti
19
Ilad Alavi Darazam
20
Luis M. Allende
21
Rebeca Alonso-Arias
22
Andrés Augusto Arias
23
Gokhan Aytekin
24
Peter Bergman
25
Simone Bondesan
26
Yenan T. Bryceson
27
Ingrid G. Bustos
28
Oscar Cabrera-Marante
29
Sheila Carcel
30
Paola Carrera
31
Giorgio Casari
32
Khalil Chaïbi
33
Roger Colobran
34
Antonio Condino-Neto
ORCID: 0000-0002-1069-3117
35
Laura E. Covill
36
Ottavia M. Delmonte
37
Loubna El Zein
38
Carlos Flores
39
Peter K. Gregersen
40
Marta Gut
41
Filomeen Haerynck
ORCID: 0000-0001-9161-7361
42
Rabih Halwani
43
Selda Hancerli
44
Lennart Hammarström
45
Nevin Hatipoglu
46
Adem Karbuz
47
Sevgi Keles
48
Christèle Kyheng
49
Rafael Leon-Lopez
50
Jose Luis Franco
51
Davood Mansouri
52
Javier Martinez-Picado
53
Ozge Metin Akcan
54
Isabelle Migeotte
55
Pierre Emmanuel Morange
56
Guillaume Morelle
ORCID: 0000-0001-6511-1674
57
Andrea Martin-Nalda
58
Giuseppe Novelli
59
Antonio Novelli
60
Figen Palabiyik
61
Qiang Pan-Hammarström
62
Rebeca Pérez de Diego
ORCID: 0000-0001-8426-8765
63
Laura Planas-Serra
64
Daniel E. Pleguezuelo
65
Carolina Prando
66
Aurora Pujol
ORCID: 0000-0002-9606-0600
67
Luis Felipe Reyes
68
Jacques G. Rivière
69
Carlos Rodriguez-Gallego
70
Julian Rojas
71
Patrizia Rovere-Querini
72
Agatha Schlüter
73
Mohammad Shahrooei
74
Ali Sobh
75
Pere Soler-Palacin
76
Yacine Tandjaoui-Lambiotte
77
Imran Tipu
78
Cristina Tresoldi
79
Jesus Troya
80
Diederik van de Beek
81
Mayana Zatz
82
Pawel Zawadzki
83
Saleh Zaid Al-Muhsen
84
Mohammed Faraj Alosaimi
85
Fahad M. Alsohime
86
Hagit Baris-Feldman
87
Manish J. Butte
88
Stefan N. Constantinescu
89
Megan A. Cooper
90
Clifton L. Dalgard
91
Jacques Fellay
92
James R. Heath
93
Yu Lung Lau
ORCID: 0000-0002-4780-0289
94
Richard P. Lifton
95
Tom Maniatis
96
Trine H. Mogensen
97
Horst von Bernuth
98
Alban Lermine
99
Michel Vidaud
100
Anne Boland
Anahtar Kelimeler
COVID-19
Immunity
Rare variants
Type I interferon
Kurumlar
Aarhus Universitet
Aarhus Denmark
Aarhus Universitetshospital
Aarhus Denmark
Aix Marseille Université
Marseille France
Al Jalila Genomics Center
Dubai United Arab Emirates
Amsterdam Neuroscience
Amsterdam Netherlands
Centre Hospitalier Universitaire Vaudois
Lausanne Switzerland
Centre National de Recherche en Génomique Humaine
Evry France
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas
Madrid Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras
Madrid Spain
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias
Madrid Spain
Centro de Regulacion Genomica, Barcelona
Barcelona Spain
Charité – Universitätsmedizin Berlin
Berlin Germany
Columbia University
New York United States
de Duve Institute
Brussels Belgium
Division of Clinical Immunology
Stockholm Sweden
École Polytechnique Fédérale de Lausanne
Lausanne Switzerland
Faculdades Pequeno Príncipe
Curitiba Brazil
Faculty of Medicine
Mansoura Egypt
Feinstein Institute for Medical Research
Manhasset United States
Fundació Institut dInvestigació en Ciències de la Salut Germans Trias i Pujol
Badalona Spain
Gordion Bioscience Inc
Cambridge United States
Helix
San Mateo United States
Hopital Avicenne
Bobigny France
Hôpital Erasme
Brussels Belgium
Hopital La Timone
Marseille France
Hôpital Necker Enfants Malades
Paris France
Hospital de Gran Canaria Dr. Negrin
Las Palmas de Gran Canaria Spain
Hospital Universitario 12 de Octubre
Madrid Spain
Hospital Universitario Central de Asturias
Oviedo Spain
Hospital Universitario Infanta Leonor
Madrid Spain
Hospital Universitario Nuestra Senora de Candelaria
Santa Cruz de Tenerife Spain
Hospital Universitario Reina Sofia
Cordoba Spain
Hospital Universitari Vall d'Hebron
Barcelona Spain
Institució Catalana de Recerca i Estudis Avançats
Barcelona Spain
Institut d'Investigació Biomedica de Bellvitge
Hospitalet de Llobregat Spain
Institute for Systems Biology
Seattle United States
Instituto de Investigación Sanitaria del Hospital Universitario La Paz
Madrid Spain
Instituto Tecnológico y de Energías Renovables, S.A.
Granadilla de Abona Spain
IRCCS Ospedale Pediatrico Bambino Gesù
Rome Italy
IRCCS Ospedale San Raffaele
Milan Italy
İstanbul Tıp Fakültesi
Istanbul Turkey
Istituto Neurologico Mediterraneo Neuromed, Pozzilli
Pozzilli Italy
Jeffrey Modell Diagnosis and Research Centre
Ghent Belgium
Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies
Barcelona Spain
Karolinska Institutet
Stockholm Sweden
Karolinska Universitetssjukhuset
Stockholm Sweden
King Saud University
Riyadh Saudi Arabia
Konya City Hospital
Konya Turkey
KU Leuven
Leuven Belgium
Laboratoire de Biologie Médicale Multi-Sites SeqOIA
Paris France
l'Institut des Maladies Génétiques Imagine
Paris France
Loghman Hakim Educational Hospital
Tehran Iran
Ludwig Institute for Cancer Research Brussels
Brussels Belgium
Mohammed Bin Rashid University of Medicine and Health Sciences
Dubai United Arab Emirates
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda United States
National Research Institute of Tuberculosis and Lung Disease Tehran
Tehran Iran
Necmettin Erbakan Üniversitesi
Meram Turkey
New York Genome Center
New York United States
Nuffield Department of Medicine
Oxford United Kingdom
Prof. Dr. Cemil Tascioglu City Hospital
Istanbul Turkey
Research Center for Immunodeficiencies
Tehran Iran
Rockefeller University
New York United States
San Raffaele Telethon Institute for Gene Therapy
Milan Italy
SBUMS Clinical Tuberculosis and Epidemiology Research Center
Tehran Iran
Shahid Beheshti University of Medical Sciences
Tehran Iran
SIB Swiss Institute of Bioinformatics
Lausanne Switzerland
Sina Medical Complex
Ahvaz Iran
Sorbonne Université
Paris France
Tel Aviv Sourasky Medical Center
Tel Aviv-Yafo Israel
Tel Aviv University
Tel Aviv-Yafo Israel
The University of Hong Kong Li Ka Shing Faculty of Medicine
Hong Kong Hong Kong
Uniformed Services University of the Health Sciences
Bethesda United States
Universidad de Antioquia
Medellin Colombia
Universidad de La Sabana
Chía Colombia
Universidade de São Paulo
Sao Paulo Brazil
Universidad Fernando Pessoa Canarias
Santa Maria de Guia de Gran Canaria Spain
Università degli Studi di Roma "Tor Vergata"
Rome Italy
Universitat de Vic - Universitat Central de Catalunya (UVic-UCC)
Vic Spain
Università Vita-Salute San Raffaele
Milan Italy
Université Libanaise
Beirut Lebanon
Université Paris Cité
Paris France
Université Paris-Saclay
Gif-sur-Yvette France
University of California, Los Angeles
Los Angeles United States
University of Health Sciences
Istanbul Turkey
University of Management and Technology Lahore
Lahore Pakistan
University of Sharjah
Sharjah United Arab Emirates
Uniwersytet im. Adama Mickiewicza w Poznaniu
Poznan Poland
Vall d'Hebron Institut de Recerca
Barcelona Spain
Walloon Excellence in Life Sciences and Biotechnology (WELBIO)
Brussels Belgium
Washington University School of Medicine in St. Louis
St. Louis United States
Yale School of Medicine
New Haven United States
Metrikler
40
Atıf
100
Yazar
4
Anahtar Kelime