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

A. Ingason, D. Rujescu, S. Cichon, E. Sigurdsson, T. Sigmundsson, O. P.H. Pietiläinen, J. E. Buizer-Voskamp, E. Strengman, C. Francks, P. Muglia, A. Gylfason, O. Gustafsson, P. I. Olason, S. Steinberg, T. Hansen, K. D. Jakobsen, H. B. Rasmussen, I. Giegling, H. J. Möller, A. HartmannC. Crombie, G. Fraser, N. Walker, J. Lonnqvist, J. Suvisaari, A. Tuulio-Henriksson, E. Bramon, L. A. Kiemeney, B. Franke, R. Murray, E. Vassos, T. Toulopoulou, T. W. Mühleisen, S. Tosato, M. Ruggeri, S. Djurovic, O. A. Andreassen, Z. Zhang, T. Werge, R. A. Ophoff, M. Rietschel, M. M. Nöthen, H. Petursson, H. Stefansson, L. Peltonen, D. Collier, K. Stefansson, D. M.St Clair

Research output: Contribution to journalArticlepeer-review

175 Citations (Scopus)


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 (P0.007) and deletions in 0.12 % of cases and 0.04% of controls (P0.05). The region can be divided into three intervals defined by flanking low copy repeats. Duplications spanning intervals I and II showed the most significant (P0.00010) 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.

Original languageEnglish
Pages (from-to)17-25
Number of pages9
JournalMolecular Psychiatry
Issue number1
Publication statusPublished - 1 Jan 2011

Bibliographical note

Funding Information:
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).

Other keywords

  • 16p13.1
  • CNV
  • duplication
  • schizophrenia
  • Adolescent
  • Adult
  • Case-Control Studies
  • Child
  • Chromosome Aberrations
  • Chromosome Mapping
  • Chromosomes, Human, Pair 16
  • DNA Copy Number Variations
  • Female
  • Humans
  • Male
  • Reference Values
  • Segmental Duplications, Genomic
  • Sequence Deletion
  • Young Adult


Dive into the research topics of 'Copy number variations of chromosome 16p13.1 region associated with schizophrenia'. Together they form a unique fingerprint.

Cite this