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Network analysis of genome-wide association studies for drug target prioritisation
Institution:1. European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge, CB10 1SD, UK;2. Open Targets, Wellcome Genome Campus, Cambridge, CB10 1SA, UK;3. Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, 8093, Switzerland
Abstract:Over the past decades, genome-wide association studies (GWAS) have led to a dramatic expansion of genetic variants implicated with human traits and diseases. These advances are expected to result in new drug targets but the identification of causal genes and the cell biology underlying human diseases from GWAS remains challenging. Here, we review protein interaction network-based methods to analyse GWAS data. These approaches can rank candidate drug targets at GWAS-associated loci or among interactors of disease genes without direct genetic support. These methods identify the cell biology affected in common across diseases, offering opportunities for drug repurposing, as well as be combined with expression data to identify focal tissues and cell types. Going forward, we expect that these methods will further improve from advances in the characterisation of context specific interaction networks and the joint analysis of rare and common genetic signals.
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