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10.1093/hmg/ddab049

http://scihub22266oqcxt.onion/10.1093/hmg/ddab049
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33577681!7928862!33577681
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suck abstract from ncbi


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pmid33577681      Hum+Mol+Genet 2021 ; 30 (3-4): 294-304
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  • Integration of genetically regulated gene expression and pharmacological library provides therapeutic drug candidates #MMPMID33577681
  • Konuma T; Ogawa K; Okada Y
  • Hum Mol Genet 2021[Apr]; 30 (3-4): 294-304 PMID33577681show ga
  • Approaches toward new therapeutics using disease genomics, such as genome-wide association study (GWAS), are anticipated. Here, we developed Trans-Phar [integration of transcriptome-wide association study (TWAS) and pharmacological database], achieving in silico screening of compounds from a large-scale pharmacological database (L1000 Connectivity Map), which have inverse expression profiles compared with tissue-specific genetically regulated gene expression. Firstly we confirmed the statistical robustness by the application of the null GWAS data and enrichment in the true-positive drug-disease relationships by the application of UK-Biobank GWAS summary statistics in broad disease categories, then we applied the GWAS summary statistics of large-scale European meta-analysis (17 traits; naverage = 201 849) and the hospitalized COVID-19 (n = 900 687), which has urgent need for drug development. We detected potential therapeutic compounds as well as anisomycin in schizophrenia (false discovery rate (FDR)-q = 0.056) and verapamil in hospitalized COVID-19 (FDR-q = 0.068) as top-associated compounds. This approach could be effective in disease genomics-driven drug development.
  • |*COVID-19 Drug Treatment[MESH]
  • |Anisomycin/pharmacology[MESH]
  • |Databases, Genetic[MESH]
  • |Databases, Pharmaceutical[MESH]
  • |Drug Development/*methods[MESH]
  • |Gene Expression Profiling[MESH]
  • |Gene Expression Regulation/*drug effects/genetics[MESH]
  • |Genome-Wide Association Study/*methods/*statistics & numerical data[MESH]
  • |Genomics/methods[MESH]
  • |Humans[MESH]
  • |Pharmaceutical Preparations[MESH]
  • |Schizophrenia/*drug therapy[MESH]
  • |Software[MESH]
  • |Transcriptome/*genetics[MESH]


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