Format

Send to

Choose Destination
Prog Neuropsychopharmacol Biol Psychiatry. 2018 Feb 2;81:187-193. doi: 10.1016/j.pnpbp.2017.10.017. Epub 2017 Oct 31.

The interaction of NOS1AP, DISC1, DAOA, and GSK3B confers susceptibility of early-onset schizophrenia in Chinese Han population.

Author information

1
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China; HuangpuDistrictMental Health Center, 1162 Qu Xi Road, Shanghai 200023, China.
2
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China.
3
Department of Psychiatry, Qingdao Mental Health Center, 299 Nanjing Road, Qingdao, Shandong 266034, China.
4
Department of Psychiatry, Hongkou District Mental Health Center, 159 Tong Xing Road, Shanghai 200083, China.
5
Department of Psychiatry, Hongkou District Mental Health Center, 159 Tong Xing Road, Shanghai 200083, China. Electronic address: wzwhk@163.com.
6
Department of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pu Jian Road, Shanghai 200127, China. Electronic address: biolpsychiatry@126.com.
7
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wan Ping Nan Road, Shanghai 200030, China. Electronic address: yizhenghui1971@163.com.

Abstract

Although many major breakthrough had identificated potential susceptibility genes for schizophrenia, the aetiology of schizophrenia is still unknown. In the present study, we focused on the N-methyl-Daspartate receptors related genes nitric oxide synthase 1 adaptor gene (NOS1AP), disrupted in schizophrenia 1 gene (DISC1), d-amino acid oxidase activator gene (DAOA), and glycogen synthase kinase 3-beta gene (GSK3B). A family-based genetic association study (459 Han Chinese subjects in 153 nuclear families) using 3 single nucleotide polymorphisms in NOS1AP, 2 in DISC1, 1 in DAOA and 1 in GSK3B was conducted. We found rs12742393 have just positive trend with schizophrenia (SCZ) (p=0.07) after FDR correction. NOS1AP mRNA and serum levels were significantly elevated in SCZ patients (p<0.001; p<0.001) compared with healthy control. However, expression Quantitative Trait Loci (eQTL) analysis have demonstrated that rs12742393 genotype were not significantly associated with the NOS1AP mRNA expression. GMDR identified a significant seven-locus interaction model involving (NOS1AP-rs348624, rs12742393, rs1415263, DISC1-rs821633, rs1000731, DAOA-rs2391191and GSK3B- rs6438552) with a good testing accuracy (0.72). Our finding suggested statistically significant role of interaction of NOS1AP, DISC1, DAOA, and GSK3B polymorphisms (NOS1AP-rs348624, rs12742393, rs1415263, DISC1-rs821633, rs1000731, DAOA-rs2391191and GSK3B-rs6438552) in EOS susceptibility.

KEYWORDS:

DAOA; DISC1; Early-onset schizophrenia; GSK3B; NOS1AP; Serum level; Single nucleotide polymorphisms; The pedigree-based generalized multifactor dimensionality reduction; mRNA

PMID:
29100974
DOI:
10.1016/j.pnpbp.2017.10.017
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center