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The druggable genome and support for target identification and validation in drug development

Finan, C; Gaulton, A; Kruger, FA; Lumbers, RT; Shah, T; Engmann, J; Galver, L; ... Casas, JP; + view all (2017) The druggable genome and support for target identification and validation in drug development. Science Translational Medicine , 9 (383) , Article eaag1166. 10.1126/scitranslmed.aag1166. Green open access

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Abstract

Target identification (determining the correct drug targets for a disease) and target validation (demonstrating an effect of target perturbation on disease biomarkers and disease end points) are important steps in drug development. Clinically relevant associations of variants in genes encoding drug targets model the effect of modifying the same targets pharmacologically. To delineate drug development (including repurposing) opportunities arising from this paradigm, we connected complex disease- and biomarker-associated loci from genome-wide association studies to an updated set of genes encoding druggable human proteins, to agents with bioactivity against these targets, and, where there were licensed drugs, to clinical indications. We used this set of genes to inform the design of a new genotyping array, which will enable association studies of druggable genes for drug target selection and validation in human disease.

Type: Article
Title: The druggable genome and support for target identification and validation in drug development
Open access status: An open access version is available from UCL Discovery
DOI: 10.1126/scitranslmed.aag1166
Publisher version: http://doi.org/10.1126/scitranslmed.aag1166
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Cell Biology, Medicine, Research & Experimental, Research & Experimental Medicine, Coronary-heart-disease, Wide Association, Mendelian Randomization, Database, Ontology, Update, Loci, Tool, Unification, Pipeline
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics > Infectious Disease Informatics
URI: https://discovery.ucl.ac.uk/id/eprint/1552793
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