Type

Journal Article

Authors

Michael Gill
Aiden Corvin
Derek Morris

Subjects

Psychiatry

Topics
neuroscience genome wide scan vasoactive intestinal peptide genes society antipsychotic drugs cyclic amp pathogenesis of schizophrenia odds ratio

Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia. (2011)

Abstract Rare 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 drugs
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Full list of authors on original publication

Michael Gill, Aiden Corvin, Derek Morris

Experts in our system

1
Michael Gill
Trinity College Dublin
Total Publications: 260
 
2
Aiden Corvin
Trinity College Dublin
Total Publications: 190
 
3
Derek Morris
Trinity College Dublin
Total Publications: 150