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Use of genome-wide association studies for drug repositioning

Nature Biotechnology volume 30, pages 317–320 (2012)Cite this article

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To the Editor:

Over the past few years, large investments have been made in genome-wide association studies (GWAS) with the expectation that some of these studies would lead to the identification of novel therapeutic modalities or allow selection of patients who would respond better to therapeutic interventions. Although the results have provided valuable biological insights for many common diseases, the translation of the genetics findings from GWAS into the clinic remains limited and a topic of intense debate. Among the factors that could explain this situation are that the road from a gene target to an approved marketed drug takes in general more than ten years and most GWAS results have only been obtained over the past four years. Furthermore, because the effect size of the common variants identified by GWAS, alone or in aggregation, is generally modest, the impact in terms of personalized, individually tailored medicine has been negligible. We present here an analysis of another potential application of GWAS data—drug repositioning. In the following study, we assess the utility of GWAS in systematically and rapidly identifying alternative or refined indications for existing drugs.

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Figure 1: Analysis pipeline.

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Acknowledgements

The authors thank K. Peters for helpful comments on this manuscript. T.P. holds a Canada Research Chair and is supported by the Canadian Institutes of Health Research (CIHR). J.B.R. is supported by the CIHR, Ministere Développement Economique, Innovation et Exportation du Québec, Fonds de la Recherche en Santé du Québec, Lady Davis Institute of Medical Research.

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Author notes

  1. Michael R Barnes & Vincent Mooser

    Present address: Present addresses: William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London, UK and Department of Pathology and Laboratory Medicine, CHUV University Hospital, Lausanne, Switzerland.,

Authors and Affiliations

  1. Computational Biology Department, Quantitative Sciences, GlaxoSmithKline, Stevenage, UK

    Philippe Sanseau, Pankaj Agarwal & Michael R Barnes

  2. Departments of Human and Medical Genetics, McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada

    Tomi Pastinen

  3. Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada

    J Brent Richards

  4. Genetics Department, Quantitative Sciences, GlaxoSmithKline, King of Prussia, Pennsylvania, USA

    Lon R Cardon & Vincent Mooser

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Correspondence to Philippe Sanseau.

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P.X.S. is a full-time employee of GlaxoSmithKline, a pharmaceutical company.

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Sanseau, P., Agarwal, P., Barnes, M. et al. Use of genome-wide association studies for drug repositioning. Nat Biotechnol 30, 317–320 (2012). https://doi.org/10.1038/nbt.2151

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