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.
authors: MRC Social, Genetic &Developmental Psychiatry Centre, Institute of Psychiatry, Psychology &Neuroscience, King's College London, London, UK.|UK National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health, South London and Maudsley Hospital, London, UK.
authors: Gerome
authors: G
authors: Breen
authors: Neuroscience Therapeutic Area, Janssen Research &Development, LLC, Titusville, New Jersey, USA.
authors: Qingqin
authors: Q
authors: Li
authors: Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.|National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.|Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors: Bryan L
authors: BL
authors: Roth
authors: Neuroscience Research Unit, Pfizer Inc, Cambridge, Massachusetts, USA.
authors: Patricio
authors: P
authors: O'Donnell
authors: H. Lundbeck A/S, Synaptic Transmission, Neuroscience Research DK, Valby, Denmark.
authors: Michael
authors: M
authors: Didriksen
authors: Department of Neuroscience, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
authors: Ricardo
authors: R
authors: Dolmetsch
authors: MRC Social, Genetic &Developmental Psychiatry Centre, Institute of Psychiatry, Psychology &Neuroscience, King's College London, London, UK.
authors: Paul F
authors: PF
authors: O'Reilly
authors: MRC Social, Genetic &Developmental Psychiatry Centre, Institute of Psychiatry, Psychology &Neuroscience, King's College London, London, UK.|UK National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health, South London and Maudsley Hospital, London, UK.
authors: Héléna A
authors: 0000-0002-5540-2707
authors: HA
authors: Gaspar
authors: Neuroscience Therapeutic Area, Janssen Research &Development, LLC, Titusville, New Jersey, USA.
authors: Husseini
authors: H
authors: Manji
authors: MRC Social, Genetic &Developmental Psychiatry Centre, Institute of Psychiatry, Psychology &Neuroscience, King's College London, London, UK.|UK National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health, South London and Maudsley Hospital, London, UK.
authors: Christopher
authors: 0000-0002-1267-8287
authors: C
authors: Huebel
authors: Department of Psychiatry, University of California San Diego, and Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
authors: John R
authors: JR
authors: Kelsoe
authors: Neuroscience Discovery and Translational Area, Pharma Research &Early Development, F. Hoffmann - La Roche, Basel, Switzerland.
authors: Dheeraj
authors: D
authors: Malhotra
authors: Institute of Psychiatry, Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy.
authors: Alessandro
authors: A
authors: Bertolino
authors: Department of Complex Trait Genetics, Centre for Neurogenomics and Cognitive Research/VU University Amsterdam, Amsterdam, the Netherlands.|Department of Clinical Genetics, VU University Medical Centre Amsterdam, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
authors: Danielle
authors: 0000-0001-7582-2365
authors: D
authors: Posthuma
authors: Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Pamela
authors: P
authors: Sklar
authors: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors: Shitij
authors: S
authors: Kapur
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors: Patrick F
authors: 0000-0002-6619-873X
authors: PF
authors: Sullivan
authors: MRC Social, Genetic &Developmental Psychiatry Centre, Institute of Psychiatry, Psychology &Neuroscience, King's College London, London, UK.|UK National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health, South London and Maudsley Hospital, London, UK.|Discovery Neuroscience Research, Eli Lilly and Company Ltd, Windlesham, Surrey, UK.
authors: David A
authors: DA
authors: Collier
authors: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.|Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors: Howard J
authors: 0000-0003-0344-9690
authors: HJ
authors: Edenberg
mesh_terms: D000818:Animals; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D001523:Mental Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011570:Psychiatry; D018570:Risk Assessment