Premium
Identification of neuroglycan C and interacting partners as potential susceptibility genes for schizophrenia in a Southern Chinese population
Author(s) -
So HonCheong,
Fong Pui Y.,
Chen Ronald Y.L.,
Hui Tomy C.K.,
Ng Mandy Y.M.,
Cherny Stacey S.,
Mak William W.M.,
Cheung Eric F.C.,
Chan Raymond C.K.,
Chen Eric Y.H.,
Li Tao,
Sham Pak C.
Publication year - 2010
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30961
Subject(s) - single nucleotide polymorphism , neuregulin 1 , genetics , snp , biology , gene , snp genotyping , erbb4 , linkage disequilibrium , candidate gene , multifactor dimensionality reduction , tag snp , genotyping , population , haplotype , genotype , medicine , signal transduction , environmental health , receptor tyrosine kinase
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 between NRG1 and ErbB4 ( P = 0.009). The gene NGC is exclusively expressed in the brain. It is implicated in neurodevelopment in rats and was previously shown to promote neurite outgrowth. Methamphetamine, a drug that may induce psychotic symptoms, was reported to alter the expression of NGC . Taken together, these results suggest that NGC may be a novel candidate gene, and neuregulin signaling pathways may play an important role in schizophrenia. © 2009 Wiley‐Liss, Inc.