早发性精神分裂症患者核心家系的后GWAS分析

项目名称： 早发性精神分裂症患者核心家系的后GWAS分析

项目编号： No.81201040

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 李文强

作者单位： 新乡医学院

项目金额： 23万元

中文摘要： 精神分裂症是一种多基因复杂疾病，遗传度高达80%。确定其易感基因有助于阐明其发病机制。全基因组关联分析（GWAS）为精神分裂症易感基因定位提供了有价值的信息，但结果易受人群因素等影响。采用相同遗传背景的大样本遗传家系对病例对照GWAS结果进行验证是提高GWAS结果可靠性的有效手段和重要途径。早发性精神分裂症危害更大、疗效更差、遗传易感性更显著。本课题组拟收集500个早发性、汉族精神分裂症患者核心家系，采用神经心理测验测试其行为和性格，采用父母教养方式量表等评估患者家庭社会心理特征，结合文献报道及课题组前期工作，从汉族精神分裂症GWAS结果中选取50个SNP位点，采用Sequenom、焦磷酸测序技术进行基因型检测，通过基于家系的遗传分析，确定这些SNP位点与汉族精神分裂症是否存在关联，分析遗传变异对神经心理的影响，分析基因与环境对其发病风险的相互作用。该结果有望为分裂症遗传学研究提供新证据。

中文关键词： 精神分裂症；基因；遗传；关联；家系

英文摘要： Schizophrenia is a kind of complex genetic diseases with many minor genes involved, and has 80% high heritability. It is the key problem for psychiatry to determine the susceptibility gene and explain the genetic mechanism of schizophrenia. There are some valuable informations provided by case-control genome-wide association studies (GWAS) for determining the susceptibility gene of schizophrenia. The results from case-control GWAS are affected by some factors, such as population stratification, design of chip, because of its own limitation. The well findings need support by other levels. Reduplication of case-control GWAS with large sample family trios is useful tool and important approach to improve the reliabity of the results from case-control GWAS. The early onset schizophrenia has more damage, poor treatment result and more possibility affected by genetic. In this study, a family-based association study was designed to confirm the association between schizophrenia and 50 SNPs selected from case-control GWAS of Han Chinese population in 500 early onset schizophrenia family trios from north Henan. Sequenom and Pyrosequencing assay will be performed for genotyping. Genetic analysis will be performed to investigate whether the SNPs are associated with schizophrenia in Han Chinese population. Neuropsychological

英文关键词： schizophrenia；gene；genetic；association；trios