Addicted To The Association Of Chromogranin B (chgb) Genes And The 15q13-q14 And Schizophrenia

Schizophrenia is a kind of mental disorder with characteristics of split of thought, affection and behavior, and incompatibility of mental activity and environment.It is concluded that schizophrenia is not a monogenic disease, but probably a polygenic disease influenced by multiple genes with small or medium risks, after a large number of epidemiology studies for long term. After linkage analysis failed to locate susceptible genes of complex diseases like schizophrenia, it is a better way to process whole-genome association studies, in which SNPs (Single Nucleotide Polymorphisms) and microsatellite marker are two important tools.In this thesis we performed an association study of CHGB (Chromogranin B) gene with schizophrenia. We selected 3 SNPs: CHGB 277T>A, CHGB 433G>A, CHGB 533A>G for case-control association analysis in Han population of Shanghai. The results of CHGB 433G>A (P=0. 0044) CHGB 533A>G (P=0. 0005) are positive. To test if the association of CHGB with schizophrenia is caused by population stratification, we performed TDT study for CHGB 277T>A, CHGB 433G>A, CHGB 533A>G in family samples from shanghai. It was found that CHGB 533A>G was positive (P=0. 019), which further demonstrated that CHGB might be related to schizophrenia. Our report is the first indication of the association of CHGB with schizophrenia in Chinese Han population.To investigate the role of the 15ql3-q14 locus in schizophrenia susceptibility, we studied three polymorphic markers D15S118, D15S1360 and D15S976, previously reported to be linked with schizophrenia, using two sets of case-control samples ascertained independently in China and Scotland. Significant association between alleles of microsatellitemarker D15S1360 and schizophrenia was found in our Chinese case-control samples (P=0.04), and replicated in an ethnically distinct Scottish case-control samples with flanking marker D15S118 (P=0. 04). Using the extended transmission disequilibrium test, we found significant transmission disequilibrium for marker D15S976 through maternal transmissions (P=0.03) in 160 Chinese family trios. Overall our data provided further evidence for the existence of a schizophrenia susceptibility locus in Chromosome 15ql3-ql4 region, and added more evidence for further study.