title: Reduced burden of very large and rare CNVs in bipolar affective disorder.
abstract: OBJECTIVE
  Large, rare chromosomal copy number variants (CNVs) have been shown to increase the risk for schizophrenia and other neuropsychiatric disorders including autism, attention-deficit hyperactivity disorder, learning difficulties, and epilepsy. Their role in bipolar disorder (BD) is less clear. There are no reports of an increase in large, rare CNVs in BD in general, but some have reported an increase in early-onset cases. We previously found that the rate of such CNVs in individuals with BD was not increased, even in early-onset cases. Our aim here was to examine the rate of large rare CNVs in BD in comparison with a new large independent reference sample from the same country.
  
  
  METHODS
  We studied the CNVs in a case-control sample consisting of 1,650 BD cases (reported previously) and 10,259 reference individuals without a known psychiatric disorder who took part in the original Wellcome Trust Case Control Consortium (WTCCC) study. The 10,259 reference individuals were affected with six non-psychiatric disorders (coronary artery disease, types 1 and 2 diabetes, hypertension, Crohn's disease, and rheumatoid arthritis). Affymetrix 500K array genotyping data were used to call the CNVs.
  
  
  RESULTS
  The rate of CNVs > 100 kb was not statistically different between cases and controls. The rate of very large (defined as > 1 Mb) and rare (< 1%) CNVs was significantly lower in patients with BD compared with the reference group. CNV loci associated with schizophrenia were not enriched in BD and, in fact, cases of BD had the lowest number of such CNVs compared with any of the WTCCC cohorts; this finding held even for the early-onset BD cases.
  
  
  CONCLUSIONS
  Schizophrenia and BD differ with respect to CNV burden and association with specific CNVs. Our findings support the hypothesis that BD is etiologically distinct from schizophrenia with respect to large, rare CNVs and the accompanying associated neurodevelopmental abnormalities.
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff.
authors.forename: Detelina
authors.initials: D
authors.lastname: Grozeva
authors.forename: George
authors.initials: G
authors.lastname: Kirov
authors.forename: Donald F
authors.initials: DF
authors.lastname: Conrad
authors.forename: Chris P
authors.initials: CP
authors.lastname: Barnes
authors.forename: Matthew
authors.initials: M
authors.lastname: Hurles
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: Nick
authors.initials: N
authors.lastname: Craddock
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D002869:Chromosome Aberrations; D015331:Cohort Studies; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000235:genetics; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult
keywords: CNV; WTCCC; bipolar disorder; schizophrenia