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    Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia.

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    Authors
    Vacic, Vladimir
    McCarthy, Shane
    Malhotra, Dheeraj
    Murray, Fiona
    Chou, Hsun-Hua
    Peoples, Aine
    Makarov, Vladimir
    Yoon, Seungtai
    Bhandari, Abhishek
    Corominas, Roser
    Iakoucheva, Lilia M
    Krastoshevsky, Olga
    Krause, Verena
    Larach-Walters, Verónica
    Welsh, David K
    Craig, David
    Kelsoe, John R
    Gershon, Elliot S
    Leal, Suzanne M
    Dell Aquila, Marie
    Morris, Derek W
    Gill, Michael
    Corvin, Aiden
    Insel, Paul A
    McClellan, Jon
    King, Mary-Claire
    Karayiorgou, Maria
    Levy, Deborah L
    DeLisi, Lynn E
    Sebat, Jonathan
    Show allShow less
    Affiliation
    Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 12824, USA.
    Issue Date
    2011-03-24
    MeSH
    Cell Line
    Chromosomes, Human, Pair 7
    Cohort Studies
    Cyclic AMP
    DNA Copy Number Variations
    Female
    Gene Dosage
    Genes, Duplicate
    Genetic Predisposition to Disease
    Genome-Wide Association Study
    Humans
    Inheritance Patterns
    Male
    Pedigree
    Receptors, Vasoactive Intestinal Peptide, Type II
    Reproducibility of Results
    Schizophrenia
    Signal Transduction
    Transcription, Genetic
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    Metadata
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    Citation
    Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia. 2011, 471 (7339):499-503 Nature
    Journal
    Nature
    URI
    http://hdl.handle.net/10147/238813
    DOI
    10.1038/nature09884
    PubMed ID
    21346763
    Abstract
    Rare copy number variants (CNVs) have a prominent role in the aetiology of schizophrenia and other neuropsychiatric disorders. Substantial risk for schizophrenia is conferred by large (>500-kilobase) CNVs at several loci, including microdeletions at 1q21.1 (ref. 2), 3q29 (ref. 3), 15q13.3 (ref. 2) and 22q11.2 (ref. 4) and microduplication at 16p11.2 (ref. 5). However, these CNVs collectively account for a small fraction (2-4%) of cases, and the relevant genes and neurobiological mechanisms are not well understood. Here we performed a large two-stage genome-wide scan of rare CNVs and report the significant association of copy number gains at chromosome 7q36.3 with schizophrenia. Microduplications with variable breakpoints occurred within a 362-kilobase region and were detected in 29 of 8,290 (0.35%) patients versus 2 of 7,431 (0.03%) controls in the combined sample. All duplications overlapped or were located within 89 kilobases upstream of the vasoactive intestinal peptide receptor gene VIPR2. VIPR2 transcription and cyclic-AMP signalling were significantly increased in cultured lymphocytes from patients with microduplications of 7q36.3. These findings implicate altered vasoactive intestinal peptide signalling in the pathogenesis of schizophrenia and indicate the VPAC2 receptor as a potential target for the development of new antipsychotic drugs.
    Item Type
    Article
    Language
    en
    ISSN
    1476-4687
    ae974a485f413a2113503eed53cd6c53
    10.1038/nature09884
    Scopus Count
    Collections
    St. James's Hospital

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