Fig. 1: Data-driven GReX (genetically regulated gene expression)-based approach for molecular target prioritization for COVID-19. | npj Genomic Medicine

Fig. 1: Data-driven GReX (genetically regulated gene expression)-based approach for molecular target prioritization for COVID-19.

From: A translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility

Fig. 1

a Multi-tissue (n = 42) transcriptome-wide association study using: (1) GWAS summary statistics from the COVID-19 Host Genetics Initiative for COVID-19 phenotypes, and (2) transcriptomic imputation models trained in the STARNET (Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task) and GTEx (Genotype-Tissue Expression) cohorts. b Gene target prioritization via integration of multi-tissue transcriptomes (17 FDR-significant tissues for COVID-19 associated hospitalization) with perturbational transcriptomic profiles from LINCS (library of integrated network-based cellular signatures) identified IL10RB as the top candidate. In a series of validation experiments we found that: (1) blood IL10RB genetically regulated gene expression (GReX) is associated with COVID-19 severity in the VA’s Million Veteran Program—“EHR validation”, (2) COVID-19 severity was associated with increased assayed IL10RB expression in patients’ blood—“in vivo validation”, and (3) increasing IL10RB expression resulted in higher SARS-CoV-2 viral load in two different model cell systems for SARS-CoV-2 infection and replication—“in vitro validation”.

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