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Review
. 2017 Dec 6:8:896.
doi: 10.3389/fphar.2017.00896. eCollection 2017.

Enhancing the Promise of Drug Repositioning through Genetics

Jayne-Louise E Pritchard  1 , Tracy A O'Mara  1 , Dylan M Glubb  1
Affiliations
Review

Enhancing the Promise of Drug Repositioning through Genetics

Jayne-Louise E Pritchard et al. Front Pharmacol. .

Abstract

The development of new drugs has become challenging as the necessary investments in time and money have increased while drug approval rates have decreased. A potential solution to this problem is drug repositioning which aims to use existing drugs to treat conditions for which they were not originally intended. One approach that may enhance the likelihood of success is to reposition drugs against a target that has a genetic basis. The multitude of genome-wide association studies (GWASs) conducted in recent years represents a large potential pool of novel targets for drug repositioning. Although trait-associated variants identified from GWAS still need to be causally linked to a target gene, recently developed functional genomic techniques, databases, and workflows are helping to remove this bottleneck. The pre-clinical validation of repositioning against these targets also needs to be carefully performed to ensure that findings are not confounded by off-target effects or limitations of the techniques used. Nevertheless, the approaches described in this review have the potential to provide a faster, cheaper and more certain route to clinical approval.

Keywords: GWAS; drug repositioning; eQTL; functional genomics; genetics; therapeutics.

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References

    1. Amberger J. S., Bocchini C. A., Schiettecatte F., Scott A. F., Hamosh A. (2015). OMIM.org: online Mendelian Inheritance in Man (OMIM(R)), an online catalog of human genes and genetic disorders. Nucleic Acids Res. 43 D789–D798. 10.1093/nar/gku1205 - DOI - PMC - PubMed
    1. Ardlie K. G., Deluca D. S., Segrè A. V., Sullivan T. J., Young T. R., Gelfand E. T., et al. (2015). The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science 348 648–660. 10.1126/science.1262110 - DOI - PMC - PubMed
    1. Barrett T., Wilhite S. E., Ledoux P., Evangelista C., Kim I. F., Tomashevsky M., et al. (2013). NCBI GEO: archive for functional genomics data sets–update. Nucleic Acids Res. 41 D991–D995. 10.1093/nar/gks1193 - DOI - PMC - PubMed
    1. Battle A., Mostafavi S., Zhu X., Potash J. B., Weissman M. M., McCormick C., et al. (2014). Characterizing the genetic basis of transcriptome diversity through RNA-sequencing of 922 individuals. Genome Res. 24 14–24. 10.1101/gr.155192.113 - DOI - PMC - PubMed
    1. Burton P. R., Clayton D. G., Cardon L. R., Craddock N., Deloukas P., Duncanson A., et al. (2007). Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat. Genet. 39 1329–1337. 10.1038/ng.2007.17 - DOI - PMC - PubMed

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