Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia
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Date
2011-03-24
Profesor/a GuÃa
Facultad/escuela
Idioma
en
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Volume Title
Publisher
Nature Research
Nombre de Curso
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CC BY 4.0
ATRIBUCIÓN 4.0 INTERNACIONAL
Deed
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https://creativecommons.org/licenses/by/4.0/deed.es
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. © 2011 Macmillan Publishers Limited. All rights reserved.
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INDEXACIÓN: SCOPUS.
Keywords
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
Citation
Nature, Volume 471, Issue 7339, Pages 499 - 503, 24 March 2011
DOI
10.1038/nature09884