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Article: Identification of neuroglycan C and interacting partners as potential susceptibility genes for schizophrenia in a Southern Chinese population

TitleIdentification of neuroglycan C and interacting partners as potential susceptibility genes for schizophrenia in a Southern Chinese population
Authors
KeywordsCSPG5
ErbB4
Genetic association
Interaction
Neuregulin-1
Issue Date2010
Citation
American Journal Of Medical Genetics, Part B: Neuropsychiatric Genetics, 2010, v. 153 n. 1, p. 103-113 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/143699
ISSN
2014 Impact Factor: 3.416
2014 SCImago Journal Rankings: 1.643
ISI Accession Number ID
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.

References

 

DC FieldValueLanguage
dc.contributor.authorSo, HCen_HK
dc.contributor.authorFong, PYen_HK
dc.contributor.authorChen, RYLen_HK
dc.contributor.authorHui, TCKen_HK
dc.contributor.authorNg, MYMen_HK
dc.contributor.authorCherny, SSen_HK
dc.contributor.authorMak, WWMen_HK
dc.contributor.authorCheung, EFCen_HK
dc.contributor.authorChan, RCKen_HK
dc.contributor.authorChen, EYHen_HK
dc.contributor.authorLi, Ten_HK
dc.contributor.authorSham, PCen_HK
dc.date.accessioned2011-12-16T08:09:36Z-
dc.date.available2011-12-16T08:09:36Z-
dc.date.issued2010en_HK
dc.identifier.citationAmerican Journal Of Medical Genetics, Part B: Neuropsychiatric Genetics, 2010, v. 153 n. 1, p. 103-113en_HK
dc.identifier.issn1552-485Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/143699-
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.en_HK
dc.relation.ispartofAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Geneticsen_HK
dc.subjectCSPG5en_HK
dc.subjectErbB4en_HK
dc.subjectGenetic associationen_HK
dc.subjectInteractionen_HK
dc.subjectNeuregulin-1en_HK
dc.titleIdentification of neuroglycan C and interacting partners as potential susceptibility genes for schizophrenia in a Southern Chinese populationen_HK
dc.typeArticleen_HK
dc.identifier.emailCherny, SS: cherny@hku.hken_HK
dc.identifier.emailChen, EYH: eyhchen@hku.hken_HK
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.authorityCherny, SS=rp00232en_HK
dc.identifier.authorityChen, EYH=rp00392en_HK
dc.identifier.authoritySham, PC=rp00459en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/ajmg.b.30961en_HK
dc.identifier.pmid19367581-
dc.identifier.scopuseid_2-s2.0-73949094711en_HK
dc.identifier.hkuros173149-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-73949094711&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume153en_HK
dc.identifier.issue1en_HK
dc.identifier.spage103en_HK
dc.identifier.epage113en_HK
dc.identifier.isiWOS:000273440500012-
dc.identifier.scopusauthoridSo, HC=37031934700en_HK
dc.identifier.scopusauthoridFong, PY=12242921700en_HK
dc.identifier.scopusauthoridChen, RYL=16635066600en_HK
dc.identifier.scopusauthoridHui, TCK=7005618911en_HK
dc.identifier.scopusauthoridNg, MYM=8367886400en_HK
dc.identifier.scopusauthoridCherny, SS=7004670001en_HK
dc.identifier.scopusauthoridMak, WWM=22934897600en_HK
dc.identifier.scopusauthoridCheung, EFC=7006522469en_HK
dc.identifier.scopusauthoridChan, RCK=35236280300en_HK
dc.identifier.scopusauthoridChen, EYH=7402315729en_HK
dc.identifier.scopusauthoridLi, T=36072008200en_HK
dc.identifier.scopusauthoridSham, PC=34573429300en_HK

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