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

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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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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).

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Correspondence to D M St Clair.

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The authors declare no conflict of interest.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website

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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) doi:10.1038/mp.2009.101

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  • 16p13.1
  • CNV
  • schizophrenia
  • duplication

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