基于网络分析的精神分裂症与双相障碍共享基因风险位点及其功能研究

项目名称： 基于网络分析的精神分裂症与双相障碍共享基因风险位点及其功能研究

项目编号： No.81460518

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 苏莉

作者单位： 广西医科大学

项目金额： 45万元

中文摘要： 精神分裂症（SCZ）和双相障碍（BD）都是重大公共卫生问题，两病存在遗传交叠，但二者共享遗传基础尚未阐明。我们前期运用网络分析构建了SCZ与BD共享分子网络，预测和优选出13个新的两病共享核心基因，通路分析显示这些基因参与多种与SCZ和BD发生机制密切相关的信号转导、细胞通讯、神经系统及免疫系统生物过程。据此，我们假设：这些核心基因遗传多态性可能对SCZ和BD的发生风险都有显著影响，它们可能通过多种生物过程参与两病共享遗传基础。拟进行如下研究：在大样本人群中进行跨疾病遗传关联研究，从人群水平验证SCZ和BD风险基因位点；然后, 结合双荧光素酶报告基因系统、RT-PCR等技术, 通过细胞实验深入研究风险位点对基因表达的影响，从而对两病共享遗传机制提出新阐释。本研究可望为建立基于生物学病因的精神疾病诊断分类系统、以及探寻精神病药物治疗靶点提供分子遗传学依据，从而促进重性精神疾病二级预防。

中文关键词： 精神分裂症；双相障碍；易感位点；生物学功能；网络分析

英文摘要： Schizophrenia (SCZ) and bipolar disorder (BD) are both major public health problems. SCZ and BD have genetic overlapping, however, the underlying genetic mechanism shared by SCZ and BD has not been clarified. We constructed a molecular network shared by SCZ and BD and then predicted and optimized thirteen new hub genes by network analysis. Pathway analysis showed that these hub genes were involved in various biological processes which are closely related to the pathological mechanism of SCZ/BD，such as signal transduction, cell communication, the nervous system and the immune system. We assume that hub genes polymorphisms is possibly significantly associated with the risk of both SCZ and BD, and they possibly participate in the shared genetic mechanism of the two diseases through many relevant biological processes. We intend to validate our hypothesis by association studies and cell experiments. Firstly, cross-disorder study design will be adopt to find out the risk SNPs which are significantly associated with SCZ and BD. Secondly, combining Dual-Luciferase reporter assay system and real-time PCR, the impact of risk loci on gene expression will be detected that can shed new lights on genetic mechanism shared by SCZ and BD. Our expected research results can provide molecular genetics evidence for establishing the diagnosis and classification system of mental diseases based on biological pathogenesis and exploring molecular therapeutic targets, thus promoting the secondary prevention of major mental diseases.

英文关键词： schizophrenia;bipolar disorder;risk SNPs;biological function;network analysis