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An organized way to drug the genome
Many drugs that are already approved for specific diseases have known protein targets, which may be relevant for other disease types as well. In addition, a systematic way of identifying druggable genes in various diseases should help streamline the process of developing new drugs for these targets, even if no specific drugs are available for them yet. Finan et al. designed a computational approach to do this, combining data from numerous existing genome-wide association studies to identify druggable proteins, connect them with known drugs where available, and facilitate the design of new targeted therapeutics.
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.
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