title: Analysis of copy number variations at 15 schizophrenia-associated loci.
abstract: BACKGROUND
  A number of copy number variants (CNVs) have been suggested as susceptibility factors for schizophrenia. For some of these the data remain equivocal, and the frequency in individuals with schizophrenia is uncertain.
  
  
  OBJECTIVE
  To determine the contribution of CNVs at 15 schizophrenia-associated loci (a) using a large new data-set of patients with schizophrenia (n = 6882) and controls (n = 6316), and (b) combining our results with those from previous studies.
  
  
  METHODS
  We used Illumina microarrays to analyse our data. Analyses were restricted to 520 766 probes common to all arrays used in the different data-sets.
  
  
  RESULTS
  We found higher rates in participants with schizophrenia than in controls for 13 of the 15 previously implicated CNVs. Six were nominally significantly associated (P<0.05) in this new data-set: deletions at 1q21.1, NRXN1, 15q11.2 and 22q11.2 and duplications at 16p11.2 and the Angelman/Prader-Willi Syndrome (AS/PWS) region. All eight AS/PWS duplications in patients were of maternal origin. When combined with published data, 11 of the 15 loci showed highly significant evidence for association with schizophrenia (P<4.1×10(-4)).
  
  
  CONCLUSIONS
  We strengthen the support for the majority of the previously implicated CNVs in schizophrenia. About 2.5% of patients with schizophrenia and 0.9% of controls carry a large, detectable CNV at one of these loci. Routine CNV screening may be clinically appropriate given the high rate of known deleterious mutations in the disorder and the comorbidity associated with these heritable mutations.
authors: Elliott Rees, MRes, James T. R. Walters, PhD, MRCPsych, Lyudmila Georgieva, PhD, Anthony R. Isles, PhD, MRC, Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK; Kimberly D. Chambert, MS, Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, Massachuetts, USA; Alexander L. Richards, PhD, Gerwyn Mahoney-Davies, BSc, Sophie E. Legge, BSc, Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK; Jennifer L. Moran, PhD, Steven A. McCarroll, PhD, Stanley Center for Psychiatric Research, The Broad Institute of MIT and Harvard, Cambridge, Massachuetts, USA; Michael C. O'Donovan, FRCPsych, PhD, Michael J. Owen, FRCPsych, PhD, George Kirov, MRCPsych, PhD, Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors: Elliott
authors: E
authors: Rees
authors: James T R
authors: JT
authors: Walters
authors: Lyudmila
authors: L
authors: Georgieva
authors: Anthony R
authors: AR
authors: Isles
authors: Kimberly D
authors: KD
authors: Chambert
authors: Alexander L
authors: AL
authors: Richards
authors: Gerwyn
authors: G
authors: Mahoney-Davies
authors: Sophie E
authors: SE
authors: Legge
authors: Jennifer L
authors: JL
authors: Moran
authors: Steven A
authors: SA
authors: McCarroll
authors: Michael C
authors: MC
authors: O'Donovan
authors: Michael J
authors: MJ
authors: Owen
authors: George
authors: G
authors: Kirov
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017204:Angelman Syndrome / Q000235:genetics; D016022:Case-Control Studies; D002872:Chromosome Deletion; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D018392:Genomic Imprinting; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D011218:Prader-Willi Syndrome / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D055815:Young Adult