Translating genome-wide association findings into new therapeutics for psychiatry

Gerome Breen, Qingqin Li, Bryan L. Roth, Patricio O'Donnell, Michael Didriksen, Ricardo Dolmetsch, Paul F. O'Reilly, Héléna A. Gaspar, Husseini Manji, Christopher Huebel, John R. Kelsoe, Dheeraj Malhotra, Alessandro Bertolino, Danielle Posthuma, Pamela Sklar, Shitij Kapur, Patrick F. Sullivan, David A. Collier, Howard J. Edenberg

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Abstract

Genome-wide association studies (GWAS) in psychiatry, once they reach sufficient sample size and power, have been enormously successful. The Psychiatric Genomics Consortium (PGC) aims for mega-analyses with sample sizes that will grow to >1 million individuals in the next 5 years. This should lead to hundreds of new findings for common genetic variants across nine psychiatric disorders studied by the PGC. The new targets discovered by GWAS have the potential to restart largely stalled psychiatric drug development pipelines, and the translation of GWAS findings into the clinic is a key aim of the recently funded phase 3 of the PGC. This is not without considerable technical challenges. These approaches complement the other main aim of GWAS studies, risk prediction approaches for improving detection, differential diagnosis, and clinical trial design. This paper outlines the motivations, technical and analytical issues, and the plans for translating PGC phase 3 findings into new therapeutics.

Original languageEnglish (US)
Pages (from-to)1392-1396
Number of pages5
JournalNature Neuroscience
Volume19
Issue number11
DOIs
StatePublished - Oct 26 2016

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Breen, G., Li, Q., Roth, B. L., O'Donnell, P., Didriksen, M., Dolmetsch, R., O'Reilly, P. F., Gaspar, H. A., Manji, H., Huebel, C., Kelsoe, J. R., Malhotra, D., Bertolino, A., Posthuma, D., Sklar, P., Kapur, S., Sullivan, P. F., Collier, D. A., & Edenberg, H. J. (2016). Translating genome-wide association findings into new therapeutics for psychiatry. Nature Neuroscience, 19(11), 1392-1396. https://doi.org/10.1038/nn.4411