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

Hon Cheong So, Pui Y. Fong, Ronald Y.L. Chen, Tomy C.K. Hui, Mandy Y.M. Ng, Stacey S. Cherny, William W.M. Mak, Eric F.C. Cheung, Raymond C.K. Chan, Eric Y.H. Chen, Tao Li, Pak C. Sham

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)103-113
Number of pages11
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume153
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

Keywords

  • CSPG5
  • ErbB4
  • Genetic association
  • Interaction
  • Neuregulin-1

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