Search For Susceptibility Genes In Schizophrenia

PartⅠSEARCH FOR SUSCEPTIBILITY GENES IN SCHIZOPHRENIASchizophrenia (SCZ; locus SCZD [MIM #181500]) is a common mental disorder with a lifetime prevalence of 1% in general polulation. The disorder is mainly characterized by psychotic symptoms such as thought, cognitive, affective, and behavior impairments. Studies of family, twin, and adoption show that it is with a heritability of 0.70–0.85 and a 10-fold increase in risk of developing the disease to siblings of probands compared to normal controls (Levinson and Mowry 2000). Although schizophrenia is obvious genetic predisposition, and the genetic factors play an important role in the etiology and pathogenesis, however, the inheritance pattern is complex and not clear. At present, it is thought that schizophrenia is a multifactorial disease with multiple susceptibility genes of middle or small effects interacting with each other and with environmental factors to influence susceptibility of the disease. Then finding of the predisposing genes of schizophrenia could not only elucidate the pathogenesissy, but also lay a foundation for genetic testing, gene therapy, and drug development. However, on account of the existence of indefinite genetic pattern, incomplete penetrance, genetic and clinical heterogeneity, such factors lead to the difficulties in replicating the massive positive association findings from the previous studies. Therefore, we adopted the positive findings from our previous whole genome association study by use of Applid Biosystem ABI Linkag Mapping Set-2 400 microsattellite markers in two DNA pools consisting of 119 schizophrenia patients and 119 controls recruited from a relatively isolated population of Shandong province of China, in which D6S289 located in JARID2 gene was found to be associated with schizophenia. Then we selected and genotyped the SNPs individually to investigate association between JARID2 and schizophrenia by high resolution melting (HRM).Objective On the basis of positive findings from our previous whole genome study of schizophrenia, JARID2 was found to be associated with schizophrenia in DNA pooling method. In order to confirm this finding, nine SNPs from JARID2 gene were selected and genotyped in schizophrenic patients and normal controls from the eastern region of Shandong peninsula in China. Methods According to the diagnostic criteria of DSM-Ⅳ, 119 schizophrenia patients and 119 controls from the eastern region of Shandong province of China were recruited. Nine SNPs within of or near JARID2 gene were genotyped by High Resolution Melting and SNaPshot genotyping methods. Allelic, genotypic and haplotypic frequencies were analyzed by use of Haploview, PLINK, UNPHASED software package. Results All SNPs were at Hardy-Weinberg equilibrium except for rs2237158. Significant differences were not found in allelic and genotypic fequences of nine SNPs between cases and controls. However, significant differences were found in three haplotypes including ATA (rs2235258,rs9654600 and rs9396590, P=0.0393), TAC (rs9654600, rs9396590 and rs2072821 P=0.038), ATAC (rs2235258, rs9654600, rs9396590 and rs2072821 P=0.0165). Conclusion The result provided further support for JARID2 gene as a susceptibility gene for schizophrenia.PartⅡSEARCH FOR SUSCEPTIBILITY GENES IN CHILDHOOD-ONSET SCHIZOPHRENIAChildhood schizophrenia (COS) is essential the same as schizophrenia in adults, but it occurs early in life even before the teen years. The symptoms of Childhood schizophrenia includes hallucinations, delusions, behavior and thought abnormalities. It is an uncommon psychiatric illness in children and hard to be recognised in early phases.At present, the etiology has been still unknown. The studies for the susceptibility gene of childhood schizophrenia have been limited so far. We carried out the association study for YAP1 gene in 112 COS families recruited from Shandong province of China.Objective According to positive findings from our previous whole genome study of schizophrenia, YAP1 was found as a candidate gene. Therefore, twelve SNPs of YAP1 were selected and genotyped in 112 families of childhood onset schizophrenia from Shandong peninsula in China to validate the association. Methods According to the diagnostic criteria of DSM-Ⅳ, 112 childhood onset schizophrenia families from Shandong province of China were recruited. Twelve SNPs of YAP1 gene were genotyped by High Resolution Melting curve and SNaPshot genotyping methods. Allelic, genotypic and haplotypic frequencies were analyzed by use of Haploview,PLINK, and UNPHASED software package. Results All SNPs were at Hardy-Weinberg equilibrium. Significant differences were found in allelice frequencies of rs7107909 (P=0.0312) and rs2846836(P=0.008). The haplotype CG between rs2282652 and rs3858420 showed significant differences(P=0.0008). Meanwhile, statistically significant differences were also found for the four, five and six loci haplotypes. Conclusion Our results support YAP1 gene as a susceptibility gene for childhood onset schizophrenia.