학술논문
A translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility
Document Type
article
Author
Georgios Voloudakis; James M. Vicari; Sanan Venkatesh; Gabriel E. Hoffman; Kristina Dobrindt; Wen Zhang; Noam D. Beckmann; Christina A. Higgins; Stathis Argyriou; Shan Jiang; Daisy Hoagland; Lina Gao; André Corvelo; Kelly Cho; Kyung Min Lee; Jiantao Bian; Jennifer S. Lee; Sudha K. Iyengar; Shiuh-Wen Luoh; Schahram Akbarian; Robert Striker; Themistocles L. Assimes; Eric E. Schadt; Julie A. Lynch; Miriam Merad; Benjamin R. tenOever; Alexander W. Charney; Mount Sinai COVID-19 Biobank; VA Million Veteran Program COVID-19 Science Initiative; Kristen J. Brennand; John F. Fullard; Panos Roussos
Source
npj Genomic Medicine, Vol 7, Iss 1, Pp 1-15 (2022)
Subject
Language
English
ISSN
2056-7944
Abstract
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.