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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.
  • Voloudakis G; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. georgios.voloudakis@mssm.edu.
  • Vicari JM; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA. georgios.voloudakis@mssm.edu.
  • Venkatesh S; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA. georgios.voloudakis@mssm.edu.
  • Hoffman GE; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. georgios.voloudakis@mssm.edu.
  • Dobrindt K; Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA. georgios.voloudakis@mssm.edu.
  • Zhang W; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. georgios.voloudakis@mssm.edu.
  • Beckmann ND; Mental Illness Research, Education, and Clinical Center (VISN 2 South), James J. Peters VA Medical Center, Bronx, NY, USA. georgios.voloudakis@mssm.edu.
  • Higgins CA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Argyriou S; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Jiang S; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Hoagland D; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Gao L; Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Corvelo A; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Cho K; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Lee KM; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Bian J; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Lee JS; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Iyengar SK; Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Luoh SW; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Akbarian S; Mental Illness Research, Education, and Clinical Center (VISN 2 South), James J. Peters VA Medical Center, Bronx, NY, USA.
  • Striker R; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Assimes TL; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Schadt EE; Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Lynch JA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Merad M; Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • tenOever BR; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Charney AW; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Brennand KJ; Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Fullard JF; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Roussos P; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
NPJ Genom Med ; 7(1): 52, 2022 Sep 05.
Article in English | MEDLINE | ID: covidwho-2008285
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.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Variants Language: English Journal: NPJ Genom Med Year: 2022 Document Type: Article Affiliation country: S41525-022-00324-x

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Topics: Variants Language: English Journal: NPJ Genom Med Year: 2022 Document Type: Article Affiliation country: S41525-022-00324-x