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

doi:10.1038/nn.4411

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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98 Citations (Scopus)

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 language	English
Pages (from-to)	1392-1396
Journal	Nature Neuroscience
Volume	19
Issue number	11
Early online date	26 Oct 2016
DOIs	https://doi.org/10.1038/nn.4411
Publication status	Published - Nov 2016

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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

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title = "Translating genome-wide association findings into new therapeutics for psychiatry",

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.",

author = "Gerome Breen and Qingqin Li and Roth, {Bryan L} and Patricio O'donnell and Michael Didriksen and Ricardo Dolmetsch and O'reilly, {Paul F} and Gaspar, {H{\'e}l{\'e}na A} and Husseini Manji and Christopher Huebel and Kelsoe, {John R} and Dheeraj Malhotra and Alessandro Bertolino and Danielle Posthuma and Pamela Sklar and Shitij Kapur and Sullivan, {Patrick F} and Collier, {David A} and Edenberg, {Howard J}",

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Breen, G, Li, Q, Roth, BL, O'donnell, P, Didriksen, M, Dolmetsch, R, O'reilly, PF , Gaspar, HA, Manji, H, Huebel, C, Kelsoe, JR, Malhotra, D, Bertolino, A, Posthuma, D, Sklar, P, Kapur, S, Sullivan, PF, Collier, DA & Edenberg, HJ 2016, 'Translating genome-wide association findings into new therapeutics for psychiatry', Nature Neuroscience, vol. 19, no. 11, pp. 1392-1396. https://doi.org/10.1038/nn.4411

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T1 - Translating genome-wide association findings into new therapeutics for psychiatry

AU - Breen, Gerome

AU - Li, Qingqin

AU - Roth, Bryan L

AU - O'donnell, Patricio

AU - Didriksen, Michael

AU - Dolmetsch, Ricardo

AU - O'reilly, Paul F

AU - Gaspar, Héléna A

AU - Manji, Husseini

AU - Huebel, Christopher

AU - Kelsoe, John R

AU - Malhotra, Dheeraj

AU - Bertolino, Alessandro

AU - Posthuma, Danielle

AU - Sklar, Pamela

AU - Kapur, Shitij

AU - Sullivan, Patrick F

AU - Collier, David A

AU - Edenberg, Howard J

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JO - Nature Neuroscience

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ER -

Translating genome-wide association findings into new therapeutics for psychiatry

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