Genetic Studies On Susceptibility Genes And Psychiatric Disorder

Psychiatric disorder is a kind of typical complex diseases caused by all sorts of internal genetic and external environment factors. The brain dysfunction results in deficiency of cognitive, emotional, spiritual and behavioral activities. A large number of population genetics studies showed that mental disorder has a clear genetic predisposition. According to candidate gene strategy, the NAPG, DLG4 and CDH7 gene were selected; the approach of case control association was taken to analyze the genetic risk of main mental disorders in Chinese Han population.NAPG gene locates in the chromosome 18p11, which plays an important role in the cells process necessary to the neurotransmission in the central nervous system. Three locus of NAPG gene were found to be associated with bipolar disorder in Europen population by Weller. In order to verify the association between NAPG gene and bipolar disorder in Chinese Han population, we selected five SNPs to genotype based on a sample of 499 bipolar patients and 465 healthy controls. Rs473938 and rs2290279 showed significant association in both allele and genotype frequencies(rs473938: Pallele = 0.0028; rs2290279: Pallele = 0.0042). Several combinations of haplotype were found to be associated with bipolar disorder. Haplotype T–A–T of rs473938–rs2290279–rs495484 was defined by confidence intervals algorithm and had a p value of 0.0038 after 100,000 permutations. In conclusion, our study supports NAPG as a candidate for susceptibility to bipolar disorder.There has been increasing evidence of an overlap in genetic susceptibility across schizophrenia and bipolar disorder recently. A sharing susceptibility gene may confer genetic risk to their pathology. A meta-analysis of large-scale linkage results shows that bipolar disorder and schizophrenia were both associated with chromosome 18. NAPG gene just locates in this position; it is worthwhile to investigate of its relevance to schizophrenia. The purpose in this study was to use the earlier positive SNPs with others to test whether they have significant distribution based on 1034 schizophrenia patients and 1034 healthy controls samples. Finally, our study did not support NAPG as a susceptible gene for schizophrenia in the Chinese Han population, NAPG may not be a risk gene common to bipolar disorder and schizophrenia in Chinese population.Among glutamate receptors, compelling scientific evidences suggest that N-Methyl-D-Aspartate(NMDA) receptor(NMDAR) mediated signal transduction is implicated in the pathophysiology of schizophrenia. DLG4 is thought to be central in organizing the NMADR signaling complex. Few association studies have been done to test association of this gene with schizophrenia and have inconsistent results. To further evaluate the importance of DLG4 in Chinese Han schizophrenia patients, we performed an association study in relatively larger Chinese samples of 893 schizophrenia patients and 611 healthy controls. No association between these seven SNPs and schizophrenia was found within our samples.Recent GWAS study revealed that CDH7 gene was significant associated with bipolar disorder in European population. Due to the fact that the same genetic risk factor can be shared by different psychiatric disorders, we examined whether CDH7 is also associated with major depressive disorder(MDD) in this study, with a large Han Chinese sample set. We carried out a 2-stage case–control study to examine the association between CDH7 and MDD in the Chinese Han population. Ten tag SNPs were genotyped using Taqman technology in 1,045 MDD patients and 1,520 healthy controls. Single-nucleotide polymorphisms with significance were additionally genotyped in another independent sample set with 576 MDD cases and 576 healthy controls. Among ten genotyped SNPs, rs1444067 and rs12605720 were found to be significantly associated with MDD(rs1444067: Pallele = 0.00571, OR=0.830; rs12605720: Pallele = 0.00321, OR=1.245). We successfully replicated these two SNPs association with independent sample sets(rs1444067: Pallele = 0.00518; rs12605720: Pallele = 0.0227). Finally we have combined these results by a meta-analysis(rs1444067: Pallele = 0.000174, OR 0.817; rs12605720: Pallele = 0.000199, OR 1.255). Our results support CDH7 to be a risk factor of MDD in the Han Chinese population.In summary, we conducted case-control study with larger sample size to investigate several candidate genes for main psychiatric disorders. The results showed that NAPG gene was associated with bipolar disorder in Chinese Han population rather than the susceptibility genes of schizophrenia. Furthermore, we excluded DLG4 gene as the susceptibility genes of schizophrenia in Chinese. We confirmed that the CDH7 gene was associated with MDD in Chinese population. This study also verified the same genetic factors can be shared by different psychiatric disorders, which was a fundamental work in revealing the mechanism of the pathology of diseases.