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Article: Identification of neuroglycan C and interacting partners as potential susceptibility genes for schizophrenia in a Southern Chinese population
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TitleIdentification of neuroglycan C and interacting partners as potential susceptibility genes for schizophrenia in a Southern Chinese population
 
AuthorsSo, HC2
Fong, PY4
Chen, RYL2
Hui, TCK2
Ng, MYM4
Cherny, SS4 2
Mak, WWM1 4
Cheung, EFC6
Chan, RCK5 2
Chen, EYH2
Li, T3
Sham, PC4 2
 
KeywordsCSPG5
ErbB4
Genetic association
Interaction
Neuregulin-1
 
Issue Date2010
 
CitationAmerican 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
 
AbstractChromosome 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.
 
ISSN1552-485X
2012 SCImago Journal Rankings: 1.406
 
DOIhttp://dx.doi.org/10.1002/ajmg.b.30961
 
ISI Accession Number IDWOS:000273440500012
Funding AgencyGrant Number
University of Hong Kong Strategic Research Theme on Genomics
Hong Kong Research Grants Council757905
Funding Information:

Hon-Cheong So and Pui Y. Fong contributed equally to this work.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorSo, HC
 
dc.contributor.authorFong, PY
 
dc.contributor.authorChen, RYL
 
dc.contributor.authorHui, TCK
 
dc.contributor.authorNg, MYM
 
dc.contributor.authorCherny, SS
 
dc.contributor.authorMak, WWM
 
dc.contributor.authorCheung, EFC
 
dc.contributor.authorChan, RCK
 
dc.contributor.authorChen, EYH
 
dc.contributor.authorLi, T
 
dc.contributor.authorSham, PC
 
dc.date.accessioned2011-12-16T08:09:36Z
 
dc.date.available2011-12-16T08:09:36Z
 
dc.date.issued2010
 
dc.description.abstractChromosome 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.natureLink_to_subscribed_fulltext
 
dc.identifier.citationAmerican 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.doihttp://dx.doi.org/10.1002/ajmg.b.30961
 
dc.identifier.epage113
 
dc.identifier.isiWOS:000273440500012
Funding AgencyGrant Number
University of Hong Kong Strategic Research Theme on Genomics
Hong Kong Research Grants Council757905
Funding Information:

Hon-Cheong So and Pui Y. Fong contributed equally to this work.

 
dc.identifier.issn1552-485X
2012 SCImago Journal Rankings: 1.406
 
dc.identifier.issue1
 
dc.identifier.pmid19367581
 
dc.identifier.scopuseid_2-s2.0-73949094711
 
dc.identifier.spage103
 
dc.identifier.urihttp://hdl.handle.net/10722/143699
 
dc.identifier.volume153
 
dc.relation.ispartofAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
 
dc.relation.referencesReferences in Scopus
 
dc.subjectCSPG5
 
dc.subjectErbB4
 
dc.subjectGenetic association
 
dc.subjectInteraction
 
dc.subjectNeuregulin-1
 
dc.titleIdentification of neuroglycan C and interacting partners as potential susceptibility genes for schizophrenia in a Southern Chinese population
 
dc.typeArticle
 
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<contributor.author>Chan, RCK</contributor.author>
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Author Affiliations
  1. Hong Kong Institute of Biotechnology
  2. The University of Hong Kong Li Ka Shing Faculty of Medicine
  3. King's College London
  4. The University of Hong Kong
  5. Institute of Psychology Chinese Academy of Sciences
  6. Castle Peak Hospital Hong Kong