TY - JOUR
T1 - A translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility
AU - VA Million Veteran Program COVID-19 Science Initiative
AU - Mount Sinai COVID-19 Biobank
AU - Voloudakis, Georgios
AU - Vicari, James M.
AU - Venkatesh, Sanan
AU - Hoffman, Gabriel E.
AU - Dobrindt, Kristina
AU - Zhang, Wen
AU - Beckmann, Noam D.
AU - Higgins, Christina A.
AU - Argyriou, Stathis
AU - Jiang, Shan
AU - Hoagland, Daisy
AU - Gao, Lina
AU - Corvelo, André
AU - Cho, Kelly
AU - Lee, Kyung Min
AU - Bian, Jiantao
AU - Lee, Jennifer S.
AU - Iyengar, Sudha K.
AU - Luoh, Shiuh Wen
AU - Akbarian, Schahram
AU - Striker, Robert
AU - Assimes, Themistocles L.
AU - Schadt, Eric E.
AU - Lynch, Julie A.
AU - Merad, Miriam
AU - tenOever, Benjamin R.
AU - Charney, Alexander W.
AU - Brennand, Kristen J.
AU - Fullard, John F.
AU - Roussos, Panos
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41525-022-00324-x
DO - 10.1038/s41525-022-00324-x
M3 - Article
AN - SCOPUS:85137685301
SN - 2056-7944
VL - 7
JO - npj Genomic Medicine
JF - npj Genomic Medicine
IS - 1
M1 - 52
ER -