Scopus
🔓 Açık Erişim YÖKSİS DOI Eşleşti
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
Genome Medicine · Aralık 2023
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.
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
Prof. Dr. 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
Prof. Dr. 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
Doç. Dr. 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
Doç. Dr. 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
Doç. Dr. 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
Prof. Dr. JALE BENGİ ÇELİK →
Makale Bilgileri
Dergi
Genome Medicine
Toplam Atıf
61 atıf
· Scopus
Yayın TarihiAralık 2023
Cilt / Sayfa15
Scopus ID2-s2.0-85160044322
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Aarhus Universitet
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Al Jalila Genomics Center
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Evry France
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Charité – Universitätsmedizin Berlin
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Ghent Belgium
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Barcelona Spain
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Stockholm Sweden
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Stockholm Sweden
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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 Cente
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
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New York United States
San Raffaele Scientific Institute
Milan Italy
San Raffaele Telethon Institute for Gene Therapy
Milan Italy
SBUMS Clinical Tuberculosis and Epidemiology Research Center
Tehran Iran
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Tehran Iran
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Lausanne Switzerland
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Ahvaz Iran
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