Identification of neuroglycan C and interacting partners as potential susceptibility genes for schizophrenia in a Southern Chinese population.
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.
Department of Psychiatry, University of Hong Kong, Hong Kong SAR, China.
Hon-Cheong
HC
So
Pui Y
PY
Fong
Ronald Y L
RY
Chen
Tomy C K
TC
Hui
Mandy Y M
MY
Ng
Stacey S
SS
Cherny
William W M
WW
Mak
Eric F C
EF
Cheung
Raymond C K
RC
Chan
Eric Y H
EY
Chen
Tao
T
Li
Pak C
PC
Sham
D016022:Case-Control Studies; D002681:China; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D020880:Neuregulins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000628:therapy*
D011508:Chondroitin Sulfate Proteoglycans; D020880:Neuregulins; C492323:neuroglycan C, human