title: A genome wide survey supports the involvement of large copy number variants in schizophrenia with and without intellectual disability.
abstract: BACKGROUND
  Copy number variants (CNVs) have been shown to play a role in schizophrenia and intellectual disability.
  
  
  METHODS
  We compared the CNV burden in 66 patients with intellectual disability and no symptoms of psychosis (ID-only) with the burden in 64 patients with intellectual disability and schizophrenia (ID + SCZ). Samples were genotyped on three plates by the Broad Institute using the Affymetrix 6.0 array.
  
  
  RESULTS
  For CNVs larger than 100 kb, there was no difference in the CNV burden of ID-only and ID + SCZ. In contrast, the number of duplications larger than 1 Mb was increased in ID + SCZ compared to ID-only. We detected seven large duplications and two large deletions at chromosome 15q11.2 (18.5-20.1 Mb) which were all present in patients with ID + SCZ. The involvement of this region in schizophrenia was confirmed in Scottish samples from the ISC study (N = 2,114; 1,130 cases and 984 controls). Finally, one of the patients with schizophrenia and low IQ carrying a duplication at 15q11.2, is a member of a previously described pedigree with multiple cases of mild intellectual disability, schizophrenia, hearing impairment, retinitis pigmentosa and cataracts. DNA samples were available for 11 members of this family and the duplication was present in all 10 affected individuals and was absent in an unaffected individual.
  
  
  CONCLUSIONS
  Duplications at 15q11.2 (18.5-20.1 Mb) are highly prevalent in a severe group of patients characterized by intellectual disability and comorbid schizophrenia. It is also associated with a phenotype that includes schizophrenia, low IQ, hearing and visual impairments resembling the spectrum of symptoms described in "ciliopathies."
authors.affiliation: Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands; Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Eske M
authors.initials: EM
authors.lastname: Derks
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ayub
authors.forename: Kimberly
authors.initials: K
authors.lastname: Chambert
authors.forename: Jurgen
authors.initials: J
authors.lastname: Del Favero
authors.forename: Mandy
authors.initials: M
authors.lastname: Johnstone
authors.forename: Stuart
authors.initials: S
authors.lastname: MacGregor
authors.forename: Alan
authors.initials: A
authors.lastname: Maclean
authors.forename: Andrew G
authors.initials: AG
authors.lastname: McKechanie
authors.forename: Allan F
authors.initials: AF
authors.lastname: McRae
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Moran
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Pickard
authors.forename: Shaun
authors.initials: S
authors.lastname: Purcell
authors.forename: Pamela
authors.initials: P
authors.lastname: Sklar
authors.forename: David M
authors.initials: DM
authors.lastname: StClair
authors.forename: Naomi R
authors.initials: NR
authors.lastname: Wray
authors.forename: Peter M
authors.initials: PM
authors.lastname: Visscher
authors.forename: Douglas H R
authors.initials: DH
authors.lastname: Blackwood
mesh_terms: D058674:Chromosome Duplication / Q000235:genetics; D020090:Chromosome Segregation / Q000235:genetics; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics; D055106:Genome-Wide Association Study; D006306:Health Surveys; D006801:Humans; D008607:Intellectual Disability / Q000150:complications* / Q000235:genetics*; D008297:Male; D010375:Pedigree; D012559:Schizophrenia / Q000150:complications* / Q000235:genetics*; D012606:Scotland
keywords: copy number variants; genetics; intellectual disability; schizophrenia