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Identification of rare mutations of the vasoactive intestinal peptide receptor 2 gene in schizophrenia

Identification of rare mutations of the vasoactive intestinal peptide receptor 2 gene in... Objective Studies showed that rare copy number variations (CNVs) encompassing the vasoactive intestinal peptide receptor 2 gene (VIPR2) were associated with schizophrenia, indicating VIPR2 is a risk gene for schizophrenia. We hypothesized that besides CNV, rare pathogenic single-nucleotide variant (SNV) or small insertion/deletion (Indel) of VIPR2 might be present in some patients and contribute to the pathogenesis of schizophrenia. Methods We performed genome-wide CNV analysis to screen CNV at the VIPR2 locus and targeted sequencing of all the exons of VIPR2 to search for SNV and indel in a sample of patients with chronic schizophrenia from Taiwan. Results We detected a 230-kb microduplication encompassing the VIPR2 in 1 out of 200 patients. Furthermore, we identified six ultrarare SNVs, including one splicing SNV and five missense SNVs, in 516 patients. In-silico analyses showed these SNVs had a damaging effect on the function of VIPR2. Conclusion Our findings support the idea that besides CNV, rare pathogenic SNVs of VIPR2 might contribute to the pathogenesis of schizophrenia in some patients. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Psychiatric Genetics Wolters Kluwer Health

Identification of rare mutations of the vasoactive intestinal peptide receptor 2 gene in schizophrenia

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Publisher
Wolters Kluwer Health
Copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
ISSN
0955-8829
eISSN
1473-5873
DOI
10.1097/ypg.0000000000000313
Publisher site
See Article on Publisher Site

Abstract

Objective Studies showed that rare copy number variations (CNVs) encompassing the vasoactive intestinal peptide receptor 2 gene (VIPR2) were associated with schizophrenia, indicating VIPR2 is a risk gene for schizophrenia. We hypothesized that besides CNV, rare pathogenic single-nucleotide variant (SNV) or small insertion/deletion (Indel) of VIPR2 might be present in some patients and contribute to the pathogenesis of schizophrenia. Methods We performed genome-wide CNV analysis to screen CNV at the VIPR2 locus and targeted sequencing of all the exons of VIPR2 to search for SNV and indel in a sample of patients with chronic schizophrenia from Taiwan. Results We detected a 230-kb microduplication encompassing the VIPR2 in 1 out of 200 patients. Furthermore, we identified six ultrarare SNVs, including one splicing SNV and five missense SNVs, in 516 patients. In-silico analyses showed these SNVs had a damaging effect on the function of VIPR2. Conclusion Our findings support the idea that besides CNV, rare pathogenic SNVs of VIPR2 might contribute to the pathogenesis of schizophrenia in some patients.

Journal

Psychiatric Genetics – Wolters Kluwer Health

Published: Jul 1, 2022

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