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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?
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.
Persistent Identifierhttp://hdl.handle.net/10722/143699
ISSN
2013 SCImago Journal Rankings: 1.676
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

 

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
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.pmid19367581en_HK
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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