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

Hdl Handle:
http://hdl.handle.net/10147/238813
Title:
Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia.
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
Affiliation:
Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 12824, USA.
Citation:
Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia. 2011, 471 (7339):499-503 Nature
Journal:
Nature
Issue Date:
24-Mar-2011
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
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
ISSN:
1476-4687

Full metadata record

DC FieldValue Language
dc.contributor.authorVacic, Vladimiren_GB
dc.contributor.authorMcCarthy, Shaneen_GB
dc.contributor.authorMalhotra, Dheerajen_GB
dc.contributor.authorMurray, Fionaen_GB
dc.contributor.authorChou, Hsun-Huaen_GB
dc.contributor.authorPeoples, Aineen_GB
dc.contributor.authorMakarov, Vladimiren_GB
dc.contributor.authorYoon, Seungtaien_GB
dc.contributor.authorBhandari, Abhisheken_GB
dc.contributor.authorCorominas, Roseren_GB
dc.contributor.authorIakoucheva, Lilia Men_GB
dc.contributor.authorKrastoshevsky, Olgaen_GB
dc.contributor.authorKrause, Verenaen_GB
dc.contributor.authorLarach-Walters, Verónicaen_GB
dc.contributor.authorWelsh, David Ken_GB
dc.contributor.authorCraig, Daviden_GB
dc.contributor.authorKelsoe, John Ren_GB
dc.contributor.authorGershon, Elliot Sen_GB
dc.contributor.authorLeal, Suzanne Men_GB
dc.contributor.authorDell Aquila, Marieen_GB
dc.contributor.authorMorris, Derek Wen_GB
dc.contributor.authorGill, Michaelen_GB
dc.contributor.authorCorvin, Aidenen_GB
dc.contributor.authorInsel, Paul Aen_GB
dc.contributor.authorMcClellan, Jonen_GB
dc.contributor.authorKing, Mary-Claireen_GB
dc.contributor.authorKarayiorgou, Mariaen_GB
dc.contributor.authorLevy, Deborah Len_GB
dc.contributor.authorDeLisi, Lynn Een_GB
dc.contributor.authorSebat, Jonathanen_GB
dc.date.accessioned2012-08-15T14:19:09Z-
dc.date.available2012-08-15T14:19:09Z-
dc.date.issued2011-03-24-
dc.identifier.citationDuplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia. 2011, 471 (7339):499-503 Natureen_GB
dc.identifier.issn1476-4687-
dc.identifier.pmid21346763-
dc.identifier.doi10.1038/nature09884-
dc.identifier.urihttp://hdl.handle.net/10147/238813-
dc.description.abstractRare 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.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Natureen_GB
dc.subject.meshCell Line-
dc.subject.meshChromosomes, Human, Pair 7-
dc.subject.meshCohort Studies-
dc.subject.meshCyclic AMP-
dc.subject.meshDNA Copy Number Variations-
dc.subject.meshFemale-
dc.subject.meshGene Dosage-
dc.subject.meshGenes, Duplicate-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshGenome-Wide Association Study-
dc.subject.meshHumans-
dc.subject.meshInheritance Patterns-
dc.subject.meshMale-
dc.subject.meshPedigree-
dc.subject.meshReceptors, Vasoactive Intestinal Peptide, Type II-
dc.subject.meshReproducibility of Results-
dc.subject.meshSchizophrenia-
dc.subject.meshSignal Transduction-
dc.subject.meshTranscription, Genetic-
dc.titleDuplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia.en_GB
dc.typeArticleen
dc.contributor.departmentStanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 12824, USA.en_GB
dc.identifier.journalNatureen_GB
dc.description.provinceLeinsteren

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