title: Implication of a rare deletion at distal 16p11.2 in schizophrenia.
abstract: BACKGROUND
  Large genomic copy number variations have been implicated as strong risk factors for schizophrenia. However, the rarity of these events has created challenges for the identification of further pathogenic loci, and extremely large samples are required to provide convincing replication.
  
  
  OBJECTIVE
  To detect novel copy number variations that increase the susceptibility to schizophrenia by using 2 ethnically homogeneous discovery cohorts and replication in large samples.
  
  
  METHODS
  Genetic association study of microarray data.
  
  
  METHODS
  Samples of DNA were collected at 9 sites from different countries.
  
  
  METHODS
  Two discovery cohorts consisted of 790 cases with schizophrenia and schizoaffective disorder and 1347 controls of Ashkenazi Jewish descent and 662 parent-offspring trios from Bulgaria, of which the offspring had schizophrenia or schizoaffective disorder. Replication data sets consisted of 12,398 cases and 17,945 controls.
  
  
  METHODS
  Statistically increased rate of specific copy number variations in cases vs controls.
  
  
  RESULTS
  One novel locus was implicated: a deletion at distal 16p11.2, which does not overlap the proximal 16p11.2 locus previously reported in schizophrenia and autism. Deletions at this locus were found in 13 of 13,850 cases (0.094%) and 3 of 19,954 controls (0.015%) (odds ratio, 6.25 [95% CI, 1.78-21.93]; P = .001, Fisher exact test).
  
  
  CONCLUSIONS
  Deletions at distal 16p11.2 have been previously implicated in developmental delay and obesity. The region contains 9 genes, several of which are implicated in neurological diseases, regulation of body weight, and glucose homeostasis. A telomeric extension of the deletion, observed in about half the cases but no controls, potentially implicates an additional 8 genes. Our findings add a new locus to the list of copy number variations that increase the risk for development of schizophrenia.
authors: Division of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, New York 11004, USA.
authors: Saurav
authors: S
authors: Guha
authors: Elliott
authors: E
authors: Rees
authors: Ariel
authors: A
authors: Darvasi
authors: Dobril
authors: D
authors: Ivanov
authors: Masashi
authors: M
authors: Ikeda
authors: Sarah E
authors: SE
authors: Bergen
authors: Patrik K
authors: PK
authors: Magnusson
authors: Paul
authors: P
authors: Cormican
authors: Derek
authors: D
authors: Morris
authors: Michael
authors: M
authors: Gill
authors: Sven
authors: S
authors: Cichon
authors: Jeffrey A
authors: JA
authors: Rosenfeld
authors: Annette
authors: A
authors: Lee
authors: Peter K
authors: PK
authors: Gregersen
authors: John M
authors: JM
authors: Kane
authors: Anil K
authors: AK
authors: Malhotra
authors: Marcella
authors: M
authors: Rietschel
authors: Markus M
authors: MM
authors: Nöthen
authors: Franziska
authors: F
authors: Degenhardt
authors: Lutz
authors: L
authors: Priebe
authors: René
authors: R
authors: Breuer
authors: Jana
authors: J
authors: Strohmaier
authors: Douglas M
authors: DM
authors: Ruderfer
authors: Jennifer L
authors: JL
authors: Moran
authors: Kimberly D
authors: KD
authors: Chambert
authors: Alan R
authors: AR
authors: Sanders
authors: Jianxin
authors: J
authors: Shi
authors: Kenneth
authors: K
authors: Kendler
authors: Brien
authors: B
authors: Riley
authors: Tony
authors: T
authors: O'Neill
authors: Dermot
authors: D
authors: Walsh
authors: Dheeraj
authors: D
authors: Malhotra
authors: Aiden
authors: A
authors: Corvin
authors: Shaun
authors: S
authors: Purcell
authors: Pamela
authors: P
authors: Sklar
authors: Nakao
authors: N
authors: Iwata
authors: Christina M
authors: CM
authors: Hultman
authors: Patrick F
authors: PF
authors: Sullivan
authors: Jonathan
authors: J
authors: Sebat
authors: Shane
authors: S
authors: McCarthy
authors: Pablo V
authors: PV
authors: Gejman
authors: Douglas F
authors: DF
authors: Levinson
authors: Michael J
authors: MJ
authors: Owen
authors: Michael C
authors: MC
authors: O'Donovan
authors: Todd
authors: T
authors: Lencz
authors: George
authors: G
authors: Kirov
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D011618:Psychotic Disorders / Q000235:genetics*; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics*; D017384:Sequence Deletion