Copy number variants in Schizophrenia: Confirmation of five previous findings and new evidence for 3q29 microdeletions and VIPR2 duplications

Levinson, Douglas F., Duan, Jubao, Oh, Sang, Wang, Kai, Sanders, Alan R., Shi, Jianxin, Zhang, Nancy, Mowry, Bryan J., Olincy, Ann, Amin, Farooq, Cloninger, C. Robert, Silverman, Jeremy M., Buccola, Nancy G., Byerley, William F., Black, Donald W., Kendler, Kenneth S., Freedman, Robert, Dudbridge, Frank, Pe'er, Itsik, Hakonarson, Hakon, Bergen, Sarah E., Fanous, Ayman H., Holmans, Peter A. and Gejman, Pablo V. (2011) Copy number variants in Schizophrenia: Confirmation of five previous findings and new evidence for 3q29 microdeletions and VIPR2 duplications. Americal Journal of Psychiatry, 168 3: 302-316. doi:10.1176/appi.ajp.2010.10060876

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Author Levinson, Douglas F.
Duan, Jubao
Oh, Sang
Wang, Kai
Sanders, Alan R.
Shi, Jianxin
Zhang, Nancy
Mowry, Bryan J.
Olincy, Ann
Amin, Farooq
Cloninger, C. Robert
Silverman, Jeremy M.
Buccola, Nancy G.
Byerley, William F.
Black, Donald W.
Kendler, Kenneth S.
Freedman, Robert
Dudbridge, Frank
Pe'er, Itsik
Hakonarson, Hakon
Bergen, Sarah E.
Fanous, Ayman H.
Holmans, Peter A.
Gejman, Pablo V.
Title Copy number variants in Schizophrenia: Confirmation of five previous findings and new evidence for 3q29 microdeletions and VIPR2 duplications
Journal name Americal Journal of Psychiatry   Check publisher's open access policy
ISSN 0002-953X
Publication date 2011-03
Sub-type Article (original research)
DOI 10.1176/appi.ajp.2010.10060876
Volume 168
Issue 3
Start page 302
End page 316
Total pages 15
Place of publication United States
Publisher American Psychiatric Publishing, Inc.
Collection year 2012
Language eng
Formatted abstract
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.


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.

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.

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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2012 Collection
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Citation counts: TR Web of Science Citation Count  Cited 215 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 228 times in Scopus Article | Citations
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Created: Sat, 15 Oct 2011, 11:17:41 EST by Professor Bryan Mowry on behalf of Queensland Brain Institute