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