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


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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  1. Pe’er I, Yelensky R, Altshuler D, Daly MJ . Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genet Epidemiol 2008; 32: 381–385.

    Article  Google Scholar 

  2. Weiss LA, Shen Y, Korn JM, Arking DE, Miller DT, Fossdal R et al. Association between microdeletion and microduplication at 16p11.2 and autism. N Engl J Med 2008; 358: 667–675.

    Article  CAS  Google Scholar 

  3. Ferreira M, O’Donovan M, Meng Y, Jones I, Ruderfer D, Jones L et al. Collaborative genome-wide association analysis of 10,596 individuals supports a role for Ankyrin-G (ANK3) and the alpha-1C subunit of the L-type voltage-gated calcium channel (CACNA1C) in bipolar disorder. Nat Genet 2008; e-pub ahead of print 2008 August 17.

  4. O’Donovan M, Craddock N, Norton N, Williams H, Peirce T, Moskvina V et al. Identification of novel schizophrenia loci by genome-wide association and follow-up. Nat Genet 2008; e-pub ahead of print 2008 July 30.

  5. International Schizophrenia Consortium. Greater burden of rare copy number variants in schizophrenia. Nature 2008; 455: 237–241.

    Article  Google Scholar 

  6. Stefansson H, Rujescu D, Cichon S, Pietilainen OP, Ingason A, Steinberg S et al. Large recurrent microdeletions associated with schizophrenia. Nature 2008; 455: 232–236.

    Article  CAS  Google Scholar 

  7. Craddock N, O’Donovan MC, Owen MJ . Genome-wide association studies in psychiatry: lessons from early studies of non-psychiatric and psychiatric phenotypes. Mol Psychiatry 2008; 13: 649–653.

    Article  CAS  Google Scholar 

  8. McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J, Ioannidis JP et al. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet 2008; 9: 356–369.

    Article  CAS  Google Scholar 

  9. Chanock SJ, Manolio T, Boehnke M, Boerwinkle E, Hunter DJ, Thomas G et al. Replicating genotype-phenotype associations. Nature 2007; 447: 655–660.

    Article  CAS  Google Scholar 

  10. Manolio TA, Brooks LD, Collins FS . A HapMap harvest of insights into the genetics of common disease. J Clin Invest 2008; 118: 1590–1605.

    Article  CAS  Google Scholar 

  11. Pearson TA, Manolio TA . How to interpret a genome-wide association study. JAMA 2008; 299: 1335–1344.

    Article  CAS  Google Scholar 

  12. Altshuler D, Daly M . Guilt beyond a reasonable doubt. Nat Genet 2007; 39: 813–815.

    Article  CAS  Google Scholar 

  13. Craddock N, O’Donovan MC, Owen MJ . Phenotypic and genetic complexity of psychosis. Br J Psychiatry 2007; 190: 200–203.

    Article  Google Scholar 

  14. Manolio TA, Rodriguez LL, Brooks L, Abecasis G, Ballinger D, Daly M et al. New models of collaboration in genome-wide association studies: the Genetic Association Information Network. Nat Genet 2007; 39: 1045–1051.

    Article  CAS  Google Scholar 

  15. Craddock N, Owen MJ . Rethinking psychosis: the disadvantages of a dichotomous classification now outweigh the advantages. World Psychiatry 2007; 6: 20–27.

    Google Scholar 

  16. Hindorff LA, Junkins HA, Manolio TA . A catalog of published genome-wide association studies. Available at: Accessed 8/1/2008.

  17. Ioannidis JP, Patsopoulos NA, Evangelou E . Heterogeneity in meta-analyses of genome-wide association investigations. PLoS ONE 2007; 2: e841.

    Article  Google Scholar 

  18. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007; 316: 889–894.

    Article  CAS  Google Scholar 

  19. Rankinen T, Zuberi A, Chagnon YC, Weisnagel SJ, Argyropoulos G, Walts B et al. The human obesity gene map: the 2005 update. Obesity (Silver Spring) 2006; 14: 529–644.

    Article  Google Scholar 

  20. Witte JS . Multiple prostate cancer risk variants on 8q24. Nat Genet 2007; 39: 579–580.

    Article  CAS  Google Scholar 

  21. Marchini J, Howie B, Myers S, McVean G, Donnelly P . A new multipoint method for genome-wide association studies by imputation of genotypes. Nat Genet 2007; 39: 906–913.

    Article  CAS  Google Scholar 

  22. Lin DY, Hu Y, Huang BE . Simple and efficient analysis of disease association with missing genotype data. Am J Hum Genet 2008; 82: 444–452.

    Article  CAS  Google Scholar 

  23. Altshuler D, Brooks LD, Chakravarti A, Collins FS, Daly MJ, Donnelly P . A haplotype map of the human genome. Nature 2005; 437: 1299–1320.

    Article  Google Scholar 

  24. Frazer KA, Ballinger DG, Cox DR, Hinds DA, Stuve LL, Gibbs RA et al. A second generation human haplotype map of over 3.1 million SNPs. Nature 2007; 449: 851–861.

    Article  CAS  Google Scholar 

  25. Huxley J, Mayr E, Osmond H, Hoffer A . Schizophrenia as a Genetic Morphism. Nature 1964; 204: 220–221.

    Article  CAS  Google Scholar 

  26. Konneker T, Barnes T, Furberg H, Losh M, Bulik CM, Sullivan PF . A searchable database of genetic evidence for psychiatric disorders. Am J Med Genet B Neuropsychiatr Genet 2008; 147: 671–675.

    Article  Google Scholar 

  27. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th edn. American Psychiatric Association: Washington, DC, 1994.

  28. Gottesman II, Gould TD . The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003; 160: 636–645.

    Article  Google Scholar 

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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 ( 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 (, 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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The Psychiatric GWAS Consortium Steering Committee. A framework for interpreting genome-wide association studies of psychiatric disorders. Mol Psychiatry 14, 10–17 (2009).

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

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