biostudies-literatureVoloudakis GBLRD VANIDA NIH HHSNIA NIH HHSNIAID NIH HHSNIMH NIH HHSBrain and Behavior Research FoundationU.S. Department of Health & Human Services | NIH | National Institute of Mental HealthIcahn School of Medicine at Mount SinaiNIH HHSNIGMS NIH HHS52https://www.ebi.ac.uk/biostudies/studies/S-EPMC9441828biostudies-literatureUnknown7(1)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 virNPJ genomic medicineA translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility.PMC9441828S10 OD030463S10 OD026880R01 AG050986K08 MH122911COVID-19 Pilot GrantT32 GM062754R01 AG067025I01 BX002395R01 AG065582I01 BX004189K08MH122911R01 MH109677U01 DA04827929350T32 AI007180U01 MH116442Hoagland DBeckmann NDIyengar SKMerad MVenkatesh SDobrindt KJiang SAkbarian SLuoh SWLee JSLynch JAVA Million Veteran Program COVID-19 Science InitiativeVoloudakis GCho KCorvelo AMount Sinai COVID-19 BiobankHoffman GEArgyriou SRoussos PVicari JMBrennand KJBian JStriker RFullard JFSchadt EEZhang WHiggins CAtenOever BRCharney AWGao LLee KMAssimes TLfalseA 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 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 vir2022-01-01T00:00:00Z2022 Sep2026-05-29T19:00:51.75Z2025-02-19T03:29:10.899ZS-EPMC94418283606454310.1038/s41525-022-00324-x