npj Genomic Medicine (Sep 2022)
A translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility
- 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
Affiliations
- Georgios Voloudakis
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai
- James M. Vicari
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai
- Sanan Venkatesh
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai
- Gabriel E. Hoffman
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai
- Kristina Dobrindt
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai
- Wen Zhang
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai
- Noam D. Beckmann
- Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai
- Christina A. Higgins
- Department of Microbiology, Grossman School of Medicine, New York University
- Stathis Argyriou
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai
- Shan Jiang
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai
- Daisy Hoagland
- Department of Microbiology, Icahn School of Medicine at Mount Sinai
- Lina Gao
- Biostatistics Shared Resources, Knight Cancer Institute, Oregon Health & Science University
- André Corvelo
- New York Genome Center
- Kelly Cho
- VA Boston Healthcare System
- Kyung Min Lee
- VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System
- Jiantao Bian
- VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System
- Jennifer S. Lee
- Department of Medicine, Stanford University School of Medicine
- Sudha K. Iyengar
- Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University
- Shiuh-Wen Luoh
- VA Portland Health Care System
- Schahram Akbarian
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai
- Robert Striker
- Division of Infectious Diseases, Department of Medicine, University of Wisconsin
- Themistocles L. Assimes
- Department of Medicine, Stanford University School of Medicine
- Eric E. Schadt
- Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai
- Julie A. Lynch
- VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System
- Miriam Merad
- Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai
- Benjamin R. tenOever
- Department of Microbiology, Grossman School of Medicine, New York University
- Alexander W. Charney
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai
- Mount Sinai COVID-19 Biobank
- VA Million Veteran Program COVID-19 Science Initiative
- Kristen J. Brennand
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai
- John F. Fullard
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai
- Panos Roussos
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai
- DOI
- https://doi.org/10.1038/s41525-022-00324-x
- Journal volume & issue
-
Vol. 7,
no. 1
pp. 1 – 15
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.
