title: Maternally derived microduplications at 15q11-q13: implication of imprinted genes in psychotic illness.
abstract: OBJECTIVE
  Rare copy number variants have been implicated in different neurodevelopmental disorders, with the same copy number variants often increasing risk of more than one of these phenotypes. In a discovery sample of 22 schizophrenia patients with an early onset of illness (10-15 years of age), the authors observed in one patient a maternally derived 15q11-q13 duplication overlapping the Prader-Willi/Angelman syndrome critical region. This prompted investigation of the role of 15q11-q13 duplications in psychotic illness.
  
  
  METHODS
  The authors scanned 7,582 patients with schizophrenia or schizoaffective disorder and 41,370 comparison subjects without known psychiatric illness for copy number variants at 15q11-q13 and determined the parental origin of duplications using methylation-sensitive Southern hybridization analysis.
  
  
  RESULTS
  Duplications were found in four case patients and five comparison subjects. All four case patients had maternally derived duplications (0.05%), while only three of the five comparison duplications were maternally derived (0.007%), resulting in a significant excess of maternally derived duplications in case patients (odds ratio=7.3). This excess is compatible with earlier observations that risk for psychosis in people with Prader-Willi syndrome caused by maternal uniparental disomy is much higher than in those caused by deletion of the paternal chromosome.
  
  
  CONCLUSIONS
  These findings suggest that the presence of two maternal copies of a fragment of chromosome 15q11.2-q13.1 that overlaps with the Prader-Willi/Angelman syndrome critical region may be a rare risk factor for schizophrenia and other psychoses. Given that maternal duplications of this region are among the most consistent cytogenetic observations in autism, the findings provide further support for a shared genetic etiology between autism and psychosis.
authors.affiliation: Research Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark.
authors.forename: Andrés
authors.initials: A
authors.lastname: Ingason
authors.forename: George
authors.initials: G
authors.lastname: Kirov
authors.forename: Ina
authors.initials: I
authors.lastname: Giegling
authors.forename: Thomas
authors.initials: T
authors.lastname: Hansen
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Isles
authors.forename: Klaus D
authors.initials: KD
authors.lastname: Jakobsen
authors.forename: Kari T
authors.initials: KT
authors.lastname: Kristinsson
authors.forename: Louise
authors.initials: L
authors.lastname: le Roux
authors.forename: Omar
authors.initials: O
authors.lastname: Gustafsson
authors.forename: Nick
authors.initials: N
authors.lastname: Craddock
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Möller
authors.forename: Andrew
authors.initials: A
authors.lastname: McQuillin
authors.forename: Pierandrea
authors.initials: P
authors.lastname: Muglia
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Roel A
authors.initials: RA
authors.lastname: Ophoff
authors.forename: Srdjan
authors.initials: S
authors.lastname: Djurovic
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
authors.forename: Olli P H
authors.initials: OP
authors.lastname: Pietiläinen
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Emma
authors.initials: E
authors.lastname: Dempster
authors.forename: David A
authors.initials: DA
authors.lastname: Collier
authors.forename: David
authors.initials: D
authors.lastname: St Clair
authors.forename: Henrik B
authors.initials: HB
authors.lastname: Rasmussen
authors.forename: Birte Y
authors.initials: BY
authors.lastname: Glenthøj
authors.forename: Lambertus A
authors.initials: LA
authors.lastname: Kiemeney
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.forename: Sarah
authors.initials: S
authors.lastname: Tosato
authors.forename: Chiara
authors.initials: C
authors.lastname: Bonetto
authors.forename: Evald
authors.initials: E
authors.lastname: Saemundsen
authors.forename: Stefán J
authors.initials: SJ
authors.lastname: Hreidarsson
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Hugh
authors.initials: H
authors.lastname: Gurling
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Engilbert
authors.initials: E
authors.lastname: Sigurdsson
authors.forename: Hannes
authors.initials: H
authors.lastname: Petursson
authors.forename: Hreinn
authors.initials: H
authors.lastname: Stefansson
authors.forename: Dan
authors.initials: D
authors.lastname: Rujescu
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
authors.forename: Thomas
authors.initials: T
authors.lastname: Werge
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015139:Blotting, Southern; D002648:Child; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D003718:Denmark; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D009035:Mothers; D011218:Prader-Willi Syndrome / Q000235:genetics; D011618:Psychotic Disorders / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D024182:Uniparental Disomy / Q000235:genetics; D006113:United Kingdom; D055815:Young Adult