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Genome-wide Association Study Of Schizophrenia In Chinese Han Nationality Population

Posted on:2015-08-24Degree:MasterType:Thesis
Country:ChinaCandidate:S Y ZhuFull Text:PDF
GTID:2284330431970177Subject:Psychiatry and mental health
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Background:Schizophrenia (SCZ) is a serious disease in mental disorders and the epidemiological studies have shown that its global incidence was1%. There are many hypotheses about its etiology so far, the pathogenesis of schizophrenia and the pathological changes is unclear. It is generally believed that the complicated polygenic inheritance disease caused by genetic and external environmental factors is not fully comply with simple Mendel’s law and its genetic effect happens in consequence of the interaction of large numbers of minor genes. This genetic degree can get back to80%. In order to understand the etiology and pathogenesis of schizophrenia, researchers often explore the susceptibility genes of schizophrenia by genetics at home and abroad.Genome-wide association study (GAWs), the scope of human genome markup millions of single nucleotide polymorphisms, that can explore the relationship between schizophrenia and genetic by comparative analysis of the case group and control group to look for the associated with disease susceptibility genes. There ara many domestic and overseas researches about exploring the complex genetic polymorphism loci and genetic loci through the application of GAWs, and the maturing of the gene chip technology can provides a clue to explore genetic factors associated with the complex genetic diseases.Objection:Within the range of genetic, we screened SNPs loci which are associated with schizophrenia through the case-control DNA mix pool method. Except for biological reasons for its social, psychological pressure and less genetic risk factors in the control group, we selected the qinghai-tibet railway construction workers as healthy controls and look forward to get more positive loci. Finally, we discussed the susceptibility genes of schizophrenia of the Chinese han population.Method:We choose300cases Chinese han nationality schizophrenia patients as a group and considered300cases Qinghai-tibet railway construction workers as a control group. Firstly, we put the case group and the control group together in order to make efficient mixed DNA pools and then manufactured the high-throughput gene chip by using Affymetrix Genome-wide Human SNPS Array6.0. After that we scanned and genotyped the target group of600cases for genome-wide gene and make an allele frequence comparison about17024single nucleotide polymorphisms of DNA of the qinghai-tibet railway on schizophrenia patients and health workers. According to the genotyping, can select genes in statistically significant differences in polymorphism loci,compared with healthy controls. To confirm whether the candidate genes associated with Chinese han population of schizophrenia, we except to collect numbers of han Chinese patients with schizophrenia as sample in the future and to verify the candidate genes again which were screened out in this experiment as the suspicious sites. We have to study the pathogenesis of schizophrenia and the objective diagnostic basis, as well as the gene loci refered to various clinical symptoms and subtypes of schizophrenia, we used gene chip for genotyping gene frequence case-control correlation analysis and used P values do inspection for statistical analysis so that we can screened SNPs associated with schizophrenia.Results:After a case-control analysis of genome-wide association studies, we have screened four the SNP loci associated with schizophrenia preliminary. They are rs1710051(NRG3),rs1209328(ETV3),rs1041250(RAB7L1),rs1041250(NUCKS1), respectively. Among these SNP loci, the most significant SNP in the correlation is rs1710051(NRG3).Conclusion:1. This paper has selected4loci associated with mental illness.2. Neuromodulation protein3(NRG3) is highly correlated with schizophrenia.3. NGR3may be the susceptibility gene of schizophrenia.
Keywords/Search Tags:schizophrenia, Genome-wide association analysis, susceptibility genes, Singlenucleotide polymorphisms
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