• A Corrigendum to this article was published on 27 June 2012

This article has been updated

Abstract

Schizophrenia is a complex disorder caused by both genetic and environmental factors. Using 9,087 affected individuals, 12,171 controls and 915,354 imputed SNPs from the Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (PGC-SCZ), we estimate that 23% (s.e. = 1%) of variation in liability to schizophrenia is captured by SNPs. We show that a substantial proportion of this variation must be the result of common causal variants, that the variance explained by each chromosome is linearly related to its length (r = 0.89, P = 2.6 × 10−8), that the genetic basis of schizophrenia is the same in males and females, and that a disproportionate proportion of variation is attributable to a set of 2,725 genes expressed in the central nervous system (CNS; P = 7.6 × 10−8). These results are consistent with a polygenic genetic architecture and imply more individual SNP associations will be detected for this disease as sample size increases.

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Change history

  • 15 May 2012

    In the version of this article initially published, the citation for the CNS+ gene set was incorrectly given as reference 17. The correct reference (Raychadhuri et al.) has been added as reference 28 in the HTML and PDF versions of the article.

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Acknowledgements

We thank S.D. Gordon for technical assistance. We acknowledge funding from the Australian National Health and Medical Research Council (389892, 442915, 496688, 613672 and 613601), the Australian Research Council (DP0770096, DP1093502 and FT0991360) and the US National Institute of Mental Health (MH085812). This research utilized the Cluster Computer, which is funded by the Netherlands Scientific Organization (NWO; 480-05-003). Acknowledgments for PGC-SCZ are listed in the Supplementary Note.

Author information

Author notes

    • Matthew C Keller
    • , Peter M Visscher
    •  & Naomi R Wray

    These authors jointly directed this work.

Affiliations

  1. Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.

    • S Hong Lee
    • , Peter M Visscher
    •  & Naomi R Wray
  2. Queensland Institute of Medical Research, Brisbane, Queensland, Australia.

    • S Hong Lee
    • , Jian Yang
    • , Peter M Visscher
    •  & Naomi R Wray
  3. Department of Psychology & Neuroscience, University of Colorado Boulder, Boulder, Colorado, USA.

    • Teresa R DeCandia
    •  & Matthew C Keller
  4. Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, Colorado, USA.

    • Teresa R DeCandia
    •  & Matthew C Keller
  5. Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Stephan Ripke
  6. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard University, Cambridge, Massachusetts, USA.

    • Stephan Ripke
  7. University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia.

    • Jian Yang
    •  & Peter M Visscher
  8. Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.

    • Patrick F Sullivan
  9. Department of Agriculture and Food Systems, University of Melbourne, Melbourne, Victoria, Australia.

    • Michael E Goddard
  10. Biosciences Research Division, Department of Primary Industries, Melbourne, Victoria, Australia.

    • Michael E Goddard

Consortia

  1. The Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ)

    A full list of members is provided in the Supplementary Note.

  2. The International Schizophrenia Consortium (ISC)

    A full list of members is provided in the Supplementary Note.

  3. The Molecular Genetics of Schizophrenia Collaboration (MGS)

    A full list of members is provided in the Supplementary Note.

Authors

  1. Search for S Hong Lee in:

  2. Search for Teresa R DeCandia in:

  3. Search for Stephan Ripke in:

  4. Search for Jian Yang in:

  5. Search for Patrick F Sullivan in:

  6. Search for Michael E Goddard in:

  7. Search for Matthew C Keller in:

  8. Search for Peter M Visscher in:

  9. Search for Naomi R Wray in:

Contributions

N.R.W. and P.M.V. devised the study. S.H.L. performed all preliminary analyses on the ISC sample and final analyses on the PGC-SCZ samples. T.R.D. performed preliminary analyses on the MGS sample. M.C.K. directed preliminary analyses on the MGS sample. S.R. undertook the quality control analysis and imputation of the PGC-SCZ samples. M.E.G. and J.Y. advised on analyses and their interpretation. P.F.S. provided interpretation in the context of schizophrenia research. N.R.W., S.H.L. and P.M.V. wrote the first draft of the manuscript. All authors contributed to the final manuscript. The ISC, MGS and PGC-SCZ members collected and genotyped cases and controls.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Naomi R Wray.

Supplementary information

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    Supplementary Text and Figures

    Supplementary Tables 1–6, Supplementary Figures 1 and 2 and Supplementary Note

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DOI

https://doi.org/10.1038/ng.1108

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