Article: Identification of neuroglycan C and interacting partners as potential susceptibility genes for schizophrenia in a Southern Chinese population
| Title | Identification of neuroglycan C and interacting partners as potential susceptibility genes for schizophrenia in a Southern Chinese population | ||||||
|---|---|---|---|---|---|---|---|
| Authors | So, HC3 Fong, PY4 Chen, RYL3 Hui, TCK3 Ng, MYM4 Cherny, SS3 4 Mak, WWM1 4 Cheung, EFC6 Chan, RCK3 5 Chen, EYH3 Li, T2 Sham, PC3 4 | ||||||
| Keywords | CSPG5 ErbB4 Genetic association Interaction Neuregulin-1 | ||||||
| Issue Date | 2010 | ||||||
| Citation | American Journal Of Medical Genetics, Part B: Neuropsychiatric Genetics, 2010, v. 153 n. 1, p. 103-113 [How to Cite?] DOI: http://dx.doi.org/10.1002/ajmg.b.30961 | ||||||
| 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 betweenNRG1 and ErbB4 (P=0.009). The geneNGC is exclusively expressed in the brain. It is implicated in neurodevelopment in rats and was previously shown to promote neurite outgrowth. Methamphetamine, a drug thatmay induce psychotic symptoms, was reported to alter the expression of NGC. Taken together, these results suggest thatNGC may be a novel candidate gene, and neuregulin signaling pathways may play an important role in schizophrenia. © 2009 Wiley-Liss, Inc. | ||||||
| ISSN | 1552-485X 2011 SCImago Journal Rankings: 0.288 | ||||||
| DOI | http://dx.doi.org/10.1002/ajmg.b.30961 | ||||||
| ISI Accession Number ID | WOS:000273440500012
Funding Information: Hon-Cheong So and Pui Y. Fong contributed equally to this work. | ||||||
| References | References in Scopus |
| dc.contributor.author | So, HC | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Fong, PY | ||||||
| dc.contributor.author | Chen, RYL | ||||||
| dc.contributor.author | Hui, TCK | ||||||
| dc.contributor.author | Ng, MYM | ||||||
| dc.contributor.author | Cherny, SS | ||||||
| dc.contributor.author | Mak, WWM | ||||||
| dc.contributor.author | Cheung, EFC | ||||||
| dc.contributor.author | Chan, RCK | ||||||
| dc.contributor.author | Chen, EYH | ||||||
| dc.contributor.author | Li, T | ||||||
| dc.contributor.author | Sham, PC | ||||||
| dc.date.accessioned | 2011-12-16T08:09:36Z | ||||||
| dc.date.available | 2011-12-16T08:09:36Z | ||||||
| dc.date.issued | 2010 | ||||||
| dc.description.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 betweenNRG1 and ErbB4 (P=0.009). The geneNGC is exclusively expressed in the brain. It is implicated in neurodevelopment in rats and was previously shown to promote neurite outgrowth. Methamphetamine, a drug thatmay induce psychotic symptoms, was reported to alter the expression of NGC. Taken together, these results suggest thatNGC may be a novel candidate gene, and neuregulin signaling pathways may play an important role in schizophrenia. © 2009 Wiley-Liss, Inc. | ||||||
| dc.description.nature | Link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | American Journal Of Medical Genetics, Part B: Neuropsychiatric Genetics, 2010, v. 153 n. 1, p. 103-113 [How to Cite?] DOI: http://dx.doi.org/10.1002/ajmg.b.30961 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1002/ajmg.b.30961 | ||||||
| dc.identifier.epage | 113 | ||||||
| dc.identifier.isi | WOS:000273440500012
Funding Information: Hon-Cheong So and Pui Y. Fong contributed equally to this work. | ||||||
| dc.identifier.issn | 1552-485X 2011 SCImago Journal Rankings: 0.288 | ||||||
| dc.identifier.issue | 1 | ||||||
| dc.identifier.pmid | 19367581 | ||||||
| dc.identifier.scopus | eid_2-s2.0-73949094711 | ||||||
| dc.identifier.spage | 103 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/143699 | ||||||
| dc.identifier.volume | 153 | ||||||
| dc.relation.ispartof | American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.subject | CSPG5 | ||||||
| dc.subject | ErbB4 | ||||||
| dc.subject | Genetic association | ||||||
| dc.subject | Interaction | ||||||
| dc.subject | Neuregulin-1 | ||||||
| dc.title | Identification of neuroglycan C and interacting partners as potential susceptibility genes for schizophrenia in a Southern Chinese population | ||||||
| dc.type | Article |
Author Affiliations
- Hong Kong Inst.Biotechnol.
- King's College London
- The University of Hong Kong Li Ka Shing Faculty of Medicine
- The University of Hong Kong
- Institute of Psychology Chinese Academy of Sciences
- Castle Peak Hospital Hong Kong