Rare loss-of-function variants in type I IFN immunity genes are not associated with severe COVID-19.
Adolescent
Adult
Aged
Aged, 80 and over
COVID-19
/ genetics
Case-Control Studies
Child
Child, Preschool
Cohort Studies
Female
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Infant
Infant, Newborn
Interferon Regulatory Factor-7
/ genetics
Interferon Type I
/ genetics
Loss of Function Mutation
Male
Middle Aged
SARS-CoV-2
Severity of Illness Index
Toll-Like Receptor 3
/ genetics
Exome Sequencing
Whole Genome Sequencing
Young Adult
Genetic variation
Genetics
Infectious disease
Journal
The Journal of clinical investigation
ISSN: 1558-8238
Titre abrégé: J Clin Invest
Pays: United States
ID NLM: 7802877
Informations de publication
Date de publication:
15 07 2021
15 07 2021
Historique:
received:
19
01
2021
accepted:
25
05
2021
pubmed:
28
5
2021
medline:
23
7
2021
entrez:
27
5
2021
Statut:
ppublish
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 1,864 COVID-19 cases (713 with severe and 1,151 with mild disease) and 15,033 ancestry-matched population controls across 4 independent COVID-19 biobanks. We tested whether rare pLOF variants in these 13 genes were associated with severe COVID-19. We identified only 1 rare pLOF mutation across these genes among 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 found no evidence of association of rare LOF variants in the 13 candidate genes with severe COVID-19 outcomes.
Identifiants
pubmed: 34043590
pii: e147834
doi: 10.1172/JCI147834
pmc: PMC8279578
doi:
pii:
Substances chimiques
IRF7 protein, human
0
Interferon Regulatory Factor-7
0
Interferon Type I
0
TLR3 protein, human
0
Toll-Like Receptor 3
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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 : UpdateOf
Type : CommentIn
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