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Sci Transl Med. 2017 Mar 29;9(383). pii: eaag1166. doi: 10.1126/scitranslmed.aag1166.

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

Author information

1
Institute of Cardiovascular Science, Faculty of Population Health, University College London, London WC1E 6BT, U.K.
2
Farr Institute of Health Informatics, University College London, London WC1E 6BT, U.K.
3
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, U.K.
4
BenevolentAI, 40 Churchway, London, U.K.
5
Illumina Inc., 5200 Illumina Way, San Diego, CA 92122, USA.
6
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, U.K. jpo@md.catapult.org.uk a.hingorani@ucl.ac.uk jp.casas@ucl.ac.uk.
7
Institute of Cardiovascular Science, Faculty of Population Health, University College London, London WC1E 6BT, U.K. jpo@md.catapult.org.uk a.hingorani@ucl.ac.uk jp.casas@ucl.ac.uk.
8
Farr Institute of Health Informatics, University College London, London WC1E 6BT, U.K. jpo@md.catapult.org.uk a.hingorani@ucl.ac.uk jp.casas@ucl.ac.uk.

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.

PMID:
28356508
DOI:
10.1126/scitranslmed.aag1166
[Indexed for MEDLINE]

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