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A translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility
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 genom...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2022
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9441828/ https://www.ncbi.nlm.nih.gov/pubmed/36064543 http://dx.doi.org/10.1038/s41525-022-00324-x |
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| 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 |
| author_facet | 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 |
| author_sort | Voloudakis, Georgios |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-9441828 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2022 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-94418282022-09-06 A translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility 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 NPJ Genom Med Article 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. Nature Publishing Group UK 2022-09-05 /pmc/articles/PMC9441828/ /pubmed/36064543 http://dx.doi.org/10.1038/s41525-022-00324-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article 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 A translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility |
| title | A translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility |
| title_full | A translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility |
| title_fullStr | A translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility |
| title_full_unstemmed | A translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility |
| title_short | A translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility |
| title_sort | translational genomics approach identifies il10rb as the top candidate gene target for covid-19 susceptibility |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9441828/ https://www.ncbi.nlm.nih.gov/pubmed/36064543 http://dx.doi.org/10.1038/s41525-022-00324-x |
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