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dc.contributor.authorMORRIS, DEREKen
dc.contributor.authorCORVIN, AIDENen
dc.contributor.authorGILL, MICHAELen
dc.date.accessioned2013-08-07T15:44:26Z
dc.date.available2013-08-07T15:44:26Z
dc.date.issued2011en
dc.date.submitted2011en
dc.identifier.citationVacic V, McCarthy S, Malhotra D, Murray F, Chou HH, Peoples A, Makarov V, Yoon S, Bhandari A, Corominas R, Iakoucheva LM, Krastoshevsky O, Krause V, Larach-Walters V, Welsh DK, Craig D, Kelsoe JR, Gershon ES, Leal SM, Dell Aquila M, Morris DW, Gill M, Corvin A, Insel PA, McClellan J, King MC, Karayiorgou M, Levy DL, DeLisi LE, Sebat J, Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia., Nature, 471, 7339, 2011, 499-503en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/66914
dc.descriptionPUBLISHEDen
dc.descriptionPMID:21346763en
dc.description.abstractRare copy number variants (CNVs) play a prominent role in the etiology of schizophrenia and other neuropsychiatric disorders 1 . Substantial risk for schizophrenia is conferred by large (>500 kb) CNVs at several loci, including microdeletions at 1q21.1 2 , 3q29 3 , 15q13.3 2 and 22q11.2 4 and microduplication at 16p11.2 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 (P= 4.0?10 -5 , OR = 16.14 [3.06, ? ]). Microduplications with variable breakpoints occurred within a 362 kb region and were detected in 29 of 8,290 (0.35%) patients versus two of 7,431 (0.03%) controls in the combined sample (p-value= 5.7?10-7, odds ratio (OR) = 14.1 [3.5, 123.9]). All duplications overlapped or were located within 89 kb upstream of the vasoactive intestinal peptide receptor VIPR2. VIPR2 transcription and cyclic-AMP signaling were significantly increased in cultured lymphocytes from patients with microduplications of 7q36.3. These findings implicate altered VIP signaling in the pathogenesis of schizophrenia and suggest VIPR2 as a potential target for the development of novel antipsychotic drugsen
dc.description.sponsorshipThis study was supported by a gift from Ted and Vada Stanley to the Cold Spring Harbor Laboratory, a gift to J.S. from the Beyster family foundation, NIH grants to J.S. (MH076431, HG04222), D.L.L. (MH071523), M.C.K (MH083989), P.I. (GM66232), F.M. (HL091061), D.K.W. (MH082945), M.K. (MH061399), L.E.D (MH044245), grants to J.S., D.K.W., D.L.L. and M.C.K from NARSAD,.grants to A.C., M.G., D.M. from the Wellcome Trust (072894/Z/03/Z) and Science Foundation Ireland (08INIB1916), a career development award to D.K.W. by the Veterans Administration, and grants to D.L.L. from the Sidney R,. Baer, Jr. Foundation and Essel Foundation . We wish to thank the Genetic Association Information Network (GAIN), Molecular Genetics of Schizophrenia (MGS) and the Bipolar Genome Study (BiGS) for providing data for this study (investigators listed in the Supplementary Note ). We wish to thank Barbara Trask, Robert Malinow, and Joseph Gleeson for helpful discussionsen
dc.format.extent499-503en
dc.language.isoenen
dc.relation.ispartofseriesNatureen
dc.relation.ispartofseries471en
dc.relation.ispartofseries7339en
dc.rightsYen
dc.subjectpathogenesis of schizophreniaen
dc.subject.lcshpathogenesis of schizophreniaen
dc.titleDuplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia.en
dc.typeJournal Articleen
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/morrisdwen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/mgillen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/acorvinen
dc.identifier.rssinternalid74958en
dc.identifier.doihttp://dx.doi.org/10.1038/nature09884en
dc.subject.TCDThemeGenes & Societyen
dc.subject.TCDThemeNeuroscienceen


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