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A framework for interpreting genome-wide association studies of psychiatric disorders

Molecular Psychiatry volume 14, pages 10–17 (2009)Cite this article

Abstract

Genome-wide association studies (GWAS) have yielded a plethora of new findings in the past 3 years. By early 2009, GWAS on 47 samples of subjects with attention-deficit hyperactivity disorder, autism, bipolar disorder, major depressive disorder and schizophrenia will be completed. Taken together, these GWAS constitute the largest biological experiment ever conducted in psychiatry (59 000 independent cases and controls, 7700 family trios and >40 billion genotypes). We know that GWAS can work, and the question now is whether it will work for psychiatric disorders. In this review, we describe these studies, the Psychiatric GWAS Consortium for meta-analyses of these data, and provide a logical framework for interpretation of some of the conceivable outcomes.

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Acknowledgements

This article was written early in the history of the PGC by its coordinating committee who takes responsibility for its content. We wish to acknowledge our enduring debt to our PGC colleagues for their many contributions to this work. The members of the PGC Coordinating Committee are: Sven Cichon (University of Bonn), Nick Craddock (Cardiff University), Mark Daly (Harvard Medical School, Broad Institute), Stephen V Faraone (SUNY Upstate Medical University), Pablo V Gejman (Evanston Northwestern Healthcare and Feinberg School of Medicine, Northwestern University), John Kelsoe (University of California, San Diego), Thomas Lehner (NIMH), Douglas F Levinson (Stanford University), Audra Moran (NARSAD, ex officio), Pamela Sklar (Massachusetts General Hospital, Broad Institute) and Patrick F Sullivan (University of North Carolina at Chapel Hill). The PGC is supported by NIMH MH085520 (http://www.nimh.gov). Statistical analyses are conducted on the Genetic Cluster Computer, which is supported by the Netherlands Scientific Organization (NWO 480-05-003, PI Danielle Posthuma) along with a supplement from the Dutch Brain Foundation (http://www.hersenstichting.nl, PI Roel Ophoff). We are indebted to NARSAD for infrastructure support.

ADHD Working Group: Stephen Faraone (chair, SUNY UMU), Richard Anney (Trinity College Dublin), Jan Buitelaar (Radboud U), Josephine Elia (CHOP), Barbara Franke (Radboud U), Michael Gill (Trinity College Dublin), Hakon Hakonarson (CHOP), Lindsey Kent (St Andrews U), James McGough (UCLA), Eric Mick (MGH/Harvard), Laura Nisenbaum (Eli Lilly), Susan Smalley (UCLA), Anita Thapar (Cardiff U), Richard Todd (Wash U/St Louis, deceased) and Alexandre Todorov (Wash U/St Louis). Autism Working Group: Bernie Devlin (chair, U Pittsburgh), Mark Daly (co-chair, MGH/Harvard), Richard Anney (Trinity College Dublin), Dan Arking (Johns Hopkins U), Joseph D Buxbaum (Mt SInai School Medicine), Aravinda Chakravarti (Johns Hopkins U), Edwin Cook (U Illinois), Michael Gill (Trinity College Dublin), Leena Peltonen (U Helsinki), Joe Piven (UNC-CH), Guy Rouleau (U Montreal), Gerard Schellenberg (U Washington), Steve Scherer (U Toronto), James Sutcliffe (Vanderbilt U), Peter Szatmari (McMaster U) and Veronica Vieland (Columbus Children's Research Institute).

Bipolar Disorder Working Group: John Kelsoe (co-chair, UCSD), Pamela Sklar (co-chair, MGH/Harvard), Ole A Andreassen (U Oslo), Douglas Blackwood (U Edinburgh), Michael Boehnke (U Mich), Margit Burmeister (U Mich), Sven Cichon (U Bonn), Aiden Corvin (Trinity College Dublin), Nicholas Craddock (Cardiff U), Manuel Ferreira (MGH/Harvard), Matthew Flickinger (U Mich), Tiffany Greenwood (UCSD), Weihua Guan (U Mich), Hugh Gurling (UCL), Jun Li (U Mich), Eric Mick (MGH/Harvard), Valentina Moskvina (Cardiff U), Pierandrea Muglia (GSK), Walter Muir (U Edinburgh), Markus Noethen (U Bonn), John Nurnberger (Indiana U), Shaun Purcell (MGH/Harvard), Marcella Rietschel (CIMH, Mannheim), Douglas Ruderfer (MGH/Harvard), Nicholas Schork (UCSD), Thomas Schulze (CIMH, Mannheim), Laura Scott (U Mich), Michael Steffens (U Bonn), Ruchi Upmanyu (GSK) and Thomas Wienker (U Bonn).

Major Depressive Disorder Working Group: Patrick Sullivan (chair, UNC-CH), Douglas Blackwood (U Edinburgh), Dorret Boomsma (Vrije U Amsterdam), Sven Cichon (U Bonn), Bryan Dechairo (Pfizer), Eco de Geus (Vrije U Amsterdam), Steve Hamilton (UCSF), Witte Hoogendijk (Vrije U Amsterdam), Doug Levinson (Stanford U), Cathryn Lewis (IOP London), Susanne Lucae (MPI-P Munich), Stuart MacGregor (QIMR), Nick Martin (QIMR), Patrick McGrath (Columbia U), Peter McGuffin (IOP London), Pierandrea Muglia (GSK), Walter Muir (U Edinburgh), Markus Noethen (U Bonn), James Offord (Pfizer), Brenda Penninx (Vrije U Amsterdam), Marcella Rietschel (CIMH, Mannheim), Thomas Schulze (CIMH, Mannheim), Susan Slager (Mayo Clinic), Federica Tozzi (GSK), Peter Visscher (QIMR), AHM Willemsen (Vrije U Amsterdam) and Naomi Wray (QIMR).

Schizophrenia Working Group: Pablo Gejman (chair, ENH/NU), Ole A Andreassen (U Oslo), Douglas Blackwood (U Edinburgh), Sven Cichon (U Bonn), Aiden Corvin (Trinity College Dublin), Mark Daly (MGH/Harvard), Ayman Fanous (Washington VAMC/Georgetown/VCU), Michael Gill (Trinity College Dublin), Hugh Gurling (UCL), Peter Holmans (Cardiff U), Christina Hultman (Karolinska Institutet), Kenneth Kendler (VCU), Sari Kivikko (National Public Health Institute), Todd Lencz (LIJ), Doug Levinson (Stanford U), Anil Malhotra (LIJ), Bryan Mowry (QCMHR/UQueensland), Markus Noethen (U Bonn), Mike O’Donovan (Cardiff U), Roel Ophoff (UCLA), Michael Owen (Cardiff U), Leena Peltonen (U Helsinki), Marcella Rietschel (CIMH, Mannheim), Alan Sanders (ENH/NU), Thomas Schulze (CIMH, Mannheim), Pamela Sklar (MGH/Harvard), David St Clair (U Aberdeen), Patrick Sullivan (UNC-CH), Jaana Suvisaari (U Helsinki) and Edwin van den Oord (VCU).

Cross-Disorder Working Group: Jordan Smoller (co-chair, MGH/Harvard), Nicholas Craddock (co-chair, Cardiff U), Kenneth Kendler (co-chair, VCU), John Nurnberger (Indiana U), Roy Perlis (MGH/Harvard), Shaun Purcell (MGH/Harvard), Marcella Rietschel (CIMH, Mannheim), Susan Santangelo (MGH/Harvard) and Anita Thapar (Cardiff U).

Statistical Analysis and Computational Working Group: Mark Daly (chair, MGH/Harvard), Phillip Awadalla (U Montreal), Bernie Devlin (U Pittsburgh), Frank Dudbridge (MRC-BSU), Arnoldo Frigessi (U Oslo), Elizabeth Holliday (QCMHR/U Queensland), Peter Holmans (Cardiff U), Todd Lencz (LIJ), Doug Levinson (Stanford U), Cathryn Lewis (IOP London), Danyu Lin (UNC-CH), Valentina Moskvina (Cardiff U), Bryan Mowry (QCMHR/UQueensland), Ben Neale (MGH/Harvard), Eve Pickering (Pfizer), Danielle Posthuma (Vrije U Amsterdam), Shaun Purcell (MGH/Harvard), John Rice (Wash U/St Louis), Stephan Ripke (MPI-P Munich), Nicholas Schork (UCSD), Jonathan Sebat (CSHL), Michael Steffens (U Bonn), Jennifer Stone (MGH/Harvard), Jung-Ying Tzeng (NCSU), Veronica Vieland (Columbus Children's Research Institute) and Edwin van den Oord (VCU).

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  1. Department of Genetics, CB#7264, 4109D Neurosciences Research Building, University of North Carolina, Chapel Hill, NC, 27599-7264, USA. E-mail: pfsulliv@med.unc.edu

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The Psychiatric GWAS Consortium Steering Committee

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The Psychiatric GWAS Consortium Steering Committee. A framework for interpreting genome-wide association studies of psychiatric disorders. Mol Psychiatry 14, 10–17 (2009). https://doi.org/10.1038/mp.2008.126

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Keywords

  • genome-wide association
  • attention-deficit hyperactivity disorder
  • autism
  • bipolar disorder
  • major depressive disorder
  • schizophrenia

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