Enabling druggable genome-wide association studies for drug target selection and validation in human disease

Mapping genome-wide association studies (GWAS) findings to an updated set of genes encoding drug (and druggable) targets revealed new development and repurposing opportunities: these could be extended by deployment of genotyping arrays that ensure comprehensive capture of variation in the druggable genome, in larger samples with a broader set of disease data.

Target identification (identifying the correct drug targets for each disease) and target validation (demonstrating the effect of target perturbation on disease biomarkers and disease end-points) are essential steps in drug development. Farr researchers showed previously that biomarker and disease endpoint associations of single nucleotide polymorphisms (SNPs) in a gene encoding a drug target accurately depict the effect of modifying the same target with a pharmacological agent; others have shown that genomic support for a target is associated with a higher rate of drug development success. To delineate drug development (including repurposing) opportunities arising from this paradigm, the authors connected complex disease- and biomarker-associated loci from genome wide association studies (GWAS) to an updated set of genes encoding druggable human proteins, to compounds with bioactivity against these targets and, where these were licensed drugs, to clinical indications. The authors used this set of genes to inform the design of a new genotyping array, to enable druggable genome-wide association studies for drug target selection and validation in human disease. 

Chris Finan, Anna Gaulton, Felix Kruger, Tom Lumbers, Tina Shah, Jorgen Engmann, Luana Galver, Ryan Kelly, Anneli Karlsson, Rita Santos, John Overington, Aroon Hingorani, Juan Pablo Casas. The druggable genome and support for target identification and validation in drug development. doi: http://dx.doi.org/10.1101/066027