A translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility.
Journal
NPJ genomic medicine
ISSN: 2056-7944
Titre abrégé: NPJ Genom Med
Pays: England
ID NLM: 101685193
Informations de publication
Date de publication:
05 Sep 2022
05 Sep 2022
Historique:
received:
07
08
2021
accepted:
19
08
2022
entrez:
5
9
2022
pubmed:
6
9
2022
medline:
6
9
2022
Statut:
epublish
Résumé
Recent efforts have identified genetic loci that are associated with coronavirus disease 2019 (COVID-19) infection rates and disease outcome severity. Translating these genetic findings into druggable genes that reduce COVID-19 host susceptibility is a critical next step. Using a translational genomics approach that integrates COVID-19 genetic susceptibility variants, multi-tissue genetically regulated gene expression (GReX), and perturbagen signatures, we identified IL10RB as the top candidate gene target for COVID-19 host susceptibility. In a series of validation steps, we show that predicted GReX upregulation of IL10RB and higher IL10RB expression in COVID-19 patient blood is associated with worse COVID-19 outcomes and that in vitro IL10RB overexpression is associated with increased viral load and activation of disease-relevant molecular pathways.
Identifiants
pubmed: 36064543
doi: 10.1038/s41525-022-00324-x
pii: 10.1038/s41525-022-00324-x
pmc: PMC9441828
doi:
Types de publication
Journal Article
Langues
eng
Pagination
52Subventions
Organisme : NIMH NIH HHS
ID : U01 MH116442
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG050986
Pays : United States
Organisme : BLRD VA
ID : I01 BX004189
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM062754
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH109677
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG067025
Pays : United States
Organisme : BLRD VA
ID : I01 BX002395
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG065582
Pays : United States
Organisme : NIMH NIH HHS
ID : K08 MH122911
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA048279
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007180
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2022. The Author(s).
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