title: The druggable genome and support for target identification and validation in drug development.
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.
authors.affiliation: Institute of Cardiovascular Science, Faculty of Population Health, University College London, London WC1E 6BT, U.K.|Farr Institute of Health Informatics, University College London, London WC1E 6BT, U.K.
authors.forename: Chris
authors.identifier: 0000-0002-3319-1937
authors.initials: C
authors.lastname: Finan
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, U.K.
authors.forename: Anna
authors.identifier: 0000-0003-2634-7400
authors.initials: A
authors.lastname: Gaulton
authors.affiliation: Institute of Cardiovascular Science, Faculty of Population Health, University College London, London WC1E 6BT, U.K.|BenevolentAI, 40 Churchway, London, U.K.
authors.forename: Felix A
authors.initials: FA
authors.lastname: Kruger
authors.affiliation: Institute of Cardiovascular Science, Faculty of Population Health, University College London, London WC1E 6BT, U.K.|Farr Institute of Health Informatics, University College London, London WC1E 6BT, U.K.
authors.forename: R Thomas
authors.initials: RT
authors.lastname: Lumbers
authors.affiliation: Institute of Cardiovascular Science, Faculty of Population Health, University College London, London WC1E 6BT, U.K.|Farr Institute of Health Informatics, University College London, London WC1E 6BT, U.K.
authors.forename: Tina
authors.initials: T
authors.lastname: Shah
authors.affiliation: Institute of Cardiovascular Science, Faculty of Population Health, University College London, London WC1E 6BT, U.K.|Farr Institute of Health Informatics, University College London, London WC1E 6BT, U.K.
authors.forename: Jorgen
authors.identifier: 0000-0001-7015-7773
authors.initials: J
authors.lastname: Engmann
authors.affiliation: Illumina Inc., 5200 Illumina Way, San Diego, CA 92122, USA.
authors.forename: Luana
authors.initials: L
authors.lastname: Galver
authors.affiliation: Illumina Inc., 5200 Illumina Way, San Diego, CA 92122, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Kelley
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, U.K.
authors.forename: Anneli
authors.identifier: 0000-0001-5155-4327
authors.initials: A
authors.lastname: Karlsson
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, U.K.
authors.forename: Rita
authors.identifier: 0000-0002-5431-4756
authors.initials: R
authors.lastname: Santos
authors.affiliation: 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.|BenevolentAI, 40 Churchway, London, U.K.
authors.forename: John P
authors.initials: JP
authors.lastname: Overington
authors.affiliation: 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.|Farr Institute of Health Informatics, University College London, London WC1E 6BT, U.K.
authors.forename: Aroon D
authors.initials: AD
authors.lastname: Hingorani
authors.affiliation: 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.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Casas
mesh_terms: D055808:Drug Discovery; D058492:Drug Repositioning; D056426:Genetic Loci; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D058990:Molecular Targeted Therapy; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D057170:Translational Research, Biomedical