A translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility

VA Million Veteran Program COVID-19 Science Initiative, Mount Sinai COVID-19 Biobank

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number52
Journalnpj Genomic Medicine
Volume7
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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