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Copy number variations of chromosome 16p13.1 region associated with schizophrenia

Molecular Psychiatry volume 16, pages 17–25 (2011)Cite this article

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Abstract

Deletions and reciprocal duplications of the chromosome 16p13.1 region have recently been reported in several cases of autism and mental retardation (MR). As genomic copy number variants found in these two disorders may also associate with schizophrenia, we examined 4345 schizophrenia patients and 35 079 controls from 8 European populations for duplications and deletions at the 16p13.1 locus, using microarray data. We found a threefold excess of duplications and deletions in schizophrenia cases compared with controls, with duplications present in 0.30% of cases versus 0.09% of controls (P=0.007) and deletions in 0.12 % of cases and 0.04% of controls (P>0.05). The region can be divided into three intervals defined by flanking low copy repeats. Duplications spanning intervals I and II showed the most significant (P=0.00010) association with schizophrenia. The age of onset in duplication and deletion carriers among cases ranged from 12 to 35 years, and the majority were males with a family history of psychiatric disorders. In a single Icelandic family, a duplication spanning intervals I and II was present in two cases of schizophrenia, and individual cases of alcoholism, attention deficit hyperactivity disorder and dyslexia. Candidate genes in the region include NTAN1 and NDE1. We conclude that duplications and perhaps also deletions of chromosome 16p13.1, previously reported to be associated with autism and MR, also confer risk of schizophrenia.

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Acknowledgements

We thank the participating subjects and their relatives, and staff at the recruitment centres. We thank David Goldstein for permission to use the genotype data from the Scottish samples typed at Duke University. This work was sponsored by EU grant LSHM-CT-2006–037761 (Project SGENE). Genotyping of the Dutch samples was sponsored by NIMH funding, R01 MH078075 (to RAO).

Author information

Author notes

  1. Members of the GROUP Investigators are listed in the Appendix.

  2. See footnote

Authors and Affiliations

  1. deCODE genetics, Reykjavík, Iceland

    A Ingason, A Gylfason, O Gustafsson, P I Olason, S Steinberg, H Stefansson & K Stefansson

  2. Research Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark

    A Ingason, T Hansen, K D Jakobsen, H B Rasmussen & T Werge

  3. Division of Molecular and Clinical Neurobiology, Department of Psychiatry, Ludwig-Maximilians-University and Genetics Research Centre GmbH, Munich, Germany

    D Rujescu, I Giegling, H-J Möller & A Hartmann

  4. Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany

    S Cichon, T W Mühleisen & M M Nöthen

  5. Institute of Human Genetics, University of Bonn, Bonn, Germany

    S Cichon & M M Nöthen

  6. Department of Psychiatry, National University Hospital, Reykjavík, Iceland

    E Sigurdsson, T Sigmundsson & H Petursson

  7. Department for Molecular Medicine, National Public Health Institute, Helsinki, Finland

    O P H Pietiläinen & L Peltonen

  8. Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands

    J E Buizer-Voskamp

  9. Department of Medical Genetics and Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands

    J E Buizer-Voskamp, E Strengman & R A Ophoff

  10. Medical Genetics, GlaxoSmithKline R&D, Verona, Italy

    C Francks & P Muglia

  11. Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland

    C Crombie, G Fraser & D M St Clair

  12. Ravenscraig Hospital, Greenock, Scotland

    N Walker

  13. Department of Mental Health and Addiction, National Public Health Institute, Helsinki, Finland

    J Lonnqvist, J Suvisaari & A Tuulio-Henriksson

  14. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College, London, UK

    E Bramon, R Murray, E Vassos, T Toulopoulou & D Collier

  15. Department of Epidemiology & Biostatistics (133 EPIB)/Department of Urology (659 URO), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    L A Kiemeney

  16. Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

    B Franke

  17. Section of Psychiatry and Clinical Psychology, University of Verona, Verona, Italy

    S Tosato & M Ruggeri

  18. Institute of Psychiatry, University of Oslo, Oslo, Norway

    S Djurovic & O A Andreassen

  19. Departments of Medical Genetics and Psychiatry, Ulleval University Hospital, Oslo, Norway

    S Djurovic & O A Andreassen

  20. Department of Statistics, UCLA, Los Angeles, CA, USA

    Z Zhang

  21. UCLA Center for Neurobehavioral Genetics and Department of Human Genetics, Los Angeles, CA, USA

    R A Ophoff

  22. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim, University of Heidelberg, Mannheim, Germany

    M Rietschel

  23. Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK

    L Peltonen

  24. The Broad Institute, Cambridge, MA, USA

    L Peltonen

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  1. A Ingason
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  2. D Rujescu
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  9. C Francks
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  15. T Hansen
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  16. K D Jakobsen
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  17. H B Rasmussen
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  18. I Giegling
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  19. H-J Möller
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  20. A Hartmann
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  21. C Crombie
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  22. G Fraser
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  23. N Walker
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  24. J Lonnqvist
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  25. J Suvisaari
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  26. A Tuulio-Henriksson
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  27. E Bramon
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  28. L A Kiemeney
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  29. B Franke
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  30. R Murray
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  31. E Vassos
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  32. T Toulopoulou
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  33. T W Mühleisen
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  34. S Tosato
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  35. M Ruggeri
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  36. S Djurovic
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  37. O A Andreassen
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  38. Z Zhang
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  39. T Werge
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  40. R A Ophoff
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  41. M Rietschel
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  42. M M Nöthen
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  43. H Petursson
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  44. H Stefansson
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  45. L Peltonen
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  46. D Collier
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  47. K Stefansson
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  48. D M St Clair
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Consortia

GROUP Investigators

Corresponding author

Correspondence to D M St Clair.

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The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Molecular Psychiatry website

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Appendix

Appendix

GROUP investigators include: René S Kahn and Wiepke Cahn, Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands; Don Linszen and Lieuwe de Haan, Department of Psychiatry, Academic Medical Centre University of Amsterdam, Amsterdam, The Netherlands; Jim van Os, Lydia Krabbendam and Inez Myin-Germeys, Maastricht University Medical Centre, EURON South Limburg Mental Health Research and Teaching Network, Maastricht, The Netherlands; Durk Wiersma and Richard Bruggeman, Department of Psychiatry, University Medical Centre Groningen, University of Groningen, The Netherlands.

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Ingason, A., Rujescu, D., Cichon, S. et al. Copy number variations of chromosome 16p13.1 region associated with schizophrenia. Mol Psychiatry 16, 17–25 (2011). https://doi.org/10.1038/mp.2009.101

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