title: Copy number variants in schizophrenia: confirmation of five previous findings and new evidence for 3q29 microdeletions and VIPR2 duplications.
abstract: OBJECTIVE
  To evaluate previously reported associations of copy number variants (CNVs) with schizophrenia and to identify additional associations, the authors analyzed CNVs in the Molecular Genetics of Schizophrenia study (MGS) and additional available data.
  
  
  METHODS
  After quality control, MGS data for 3,945 subjects with schizophrenia or schizoaffective disorder and 3,611 screened comparison subjects were available for analysis of rare CNVs (<1% frequency). CNV detection thresholds were chosen that maximized concordance in 151 duplicate assays. Pointwise and genewise analyses were carried out, as well as analyses of previously reported regions. Selected regions were visually inspected and confirmed with quantitative polymerase chain reaction.
  
  
  RESULTS
  In analyses of MGS data combined with other available data sets, odds ratios of 7.5 or greater were observed for previously reported deletions in chromosomes 1q21.1, 15q13.3, and 22q11.21, duplications in 16p11.2, and exon-disrupting deletions in NRXN1. The most consistently supported candidate associations across data sets included a 1.6-Mb deletion in chromosome 3q29 (21 genes, TFRC to BDH1) that was previously described in a mild-moderate mental retardation syndrome, exonic duplications in the gene for vasoactive intestinal peptide receptor 2 (VIPR2), and exonic duplications in C16orf72. The case subjects had a modestly higher genome-wide number of gene-containing deletions (>100 kb and >1 Mb) but not duplications.
  
  
  CONCLUSIONS
  The data strongly confirm the association of schizophrenia with 1q21.1, 15q13.3, and 22q11.21 deletions, 16p11.2 duplications, and exonic NRXN1 deletions. These CNVs, as well as 3q29 deletions, are also associated with mental retardation, autism spectrum disorders, and epilepsy. Additional candidate genes and regions, including VIPR2, were identified. Study of the mechanisms underlying these associations should shed light on the pathophysiology of schizophrenia.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA 94304-5797, USA. dflev@stanford.edu
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Levinson
authors.forename: Jubao
authors.initials: J
authors.lastname: Duan
authors.forename: Sang
authors.initials: S
authors.lastname: Oh
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Alan R
authors.initials: AR
authors.lastname: Sanders
authors.forename: Jianxin
authors.initials: J
authors.lastname: Shi
authors.forename: Nancy
authors.initials: N
authors.lastname: Zhang
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Mowry
authors.forename: Ann
authors.initials: A
authors.lastname: Olincy
authors.forename: Farooq
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authors.lastname: Amin
authors.forename: C Robert
authors.initials: CR
authors.lastname: Cloninger
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Silverman
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Buccola
authors.forename: William F
authors.initials: WF
authors.lastname: Byerley
authors.forename: Donald W
authors.initials: DW
authors.lastname: Black
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kendler
authors.forename: Robert
authors.initials: R
authors.lastname: Freedman
authors.forename: Frank
authors.initials: F
authors.lastname: Dudbridge
authors.forename: Itsik
authors.initials: I
authors.lastname: Pe'er
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Bergen
authors.forename: Ayman H
authors.initials: AH
authors.lastname: Fanous
authors.forename: Peter A
authors.initials: PA
authors.lastname: Holmans
authors.forename: Pablo V
authors.initials: PV
authors.lastname: Gejman
mesh_terms: D002872:Chromosome Deletion; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data*; D006801:Humans; D012559:Schizophrenia / Q000235:genetics*