Identification of neuroglycan C and interacting partners as potential susceptibility genes for schizophrenia in a Southern Chinese population
Abstract
Chromosome 3p was reported by previous studies as one of the regions showing strong evidence of linkage with schizophrenia. We performed a fine‐mapping association study of a 6‐Mb high‐LD and gene‐rich region on 3p in a Southern Chinese sample of 489 schizophrenia patients and 519 controls to search for susceptibility genes. In the initial screen, 4 SNPs out of the 144 tag SNPs genotyped were nominally significant (P < 0.05). One of the most significant SNPs (rs3732530, P = 0.0048) was a non‐synonymous SNP in the neuroglycan C (NGC, also known as CSPG5) gene, which belongs to the neuregulin family. The gene prioritization program Endeavor ranked NGC 8th out of the 129 genes in the 6‐Mb region and the highest among the genes within the same LD block. Further genotyping of NGC revealed 3 more SNPs to be nominally associated with schizophrenia. Three other genes (NRG1, ErbB3, ErbB4) involved in the neuregulin pathways were subsequently genotyped. Interaction analysis by multifactor dimensionality reduction (MDR) revealed a significant two‐SNP interaction between NGC and NRG1 (P = 0.015) and three‐SNP interactions between NRG1 and ErbB4 (P = 0.009). The gene NGC is exclusively expressed in the brain. It is implicated in neurodevelopment in rats and was previously shown to promote neurite outgrowth. Methamphetamine, a drug that may induce psychotic symptoms, was reported to alter the expression of NGC. Taken together, these results suggest that NGC may be a novel candidate gene, and neuregulin signaling pathways may play an important role in schizophrenia. © 2009 Wiley‐Liss, Inc.
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CSPGs are involved in the pathophysiology of schizophrenia.
“Emerging evidence from human postmortem, animal model and genetic studies points to their involvement in the pathophysiology of schizophrenia (SZ).1, 2, 3, 4, 5, 6, 7”
From Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala (2015) · cites this paper as [7]
Polymorphisms of genes encoding for several CSPGs have been associated with schizophrenia.
“Finally, polymorphisms of genes encoding for several CSPGs have been associated with SZ.5, 6, 7”
From Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala (2015) · cites this paper as [7]
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- Authors
- So, H., Fong, P. Y., Chen, R. Y. L., Hui, T. C. K., Ng, M. Y. M., Cherny, S. S., Mak, W. W. M., Cheung, E. F. C., Chan, R. C. K., Chen, E. Y. H., Li, T., & Sham, P. C.
- Affiliations
- University of Hong Kong (HK)
- Castle Peak Hospital (CN)
- Chinese Academy of Sciences (CN)
- King's College London (GB)
- Corresponding author
- Sham, Pak C.
- ORCID
- Venue
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2009-12-21
- Volume
- 153B
- Issue
- 1
- Pages
- 103-113
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- OpenAlex
- W2147470501
- Cited by
- 28
- References
- 50
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 2 · 2014: 1 · 2013: 3
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repository of Institute of Psychology, Chinese Academy of Sciences (Institute of Psychology, Chinese Academy of Sciences) (submittedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- schizophrenia, neuregulin signaling, chromosome 3p, genetic susceptibility, neuregulin-1, ErbB4, HER3, gene-gene interaction, tag SNPs, southern Chinese population, methamphetamine, neurite outgrowth
- MeSH terms
- China, Humans, Chondroitin Sulfate Proteoglycans, Schizophrenia, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Neuregulins
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