拷贝数变异与精神分裂症的关联研究

项目名称： 拷贝数变异与精神分裂症的关联研究

项目编号： No.30800616

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 赵欣之

作者单位： 复旦大学

项目金额： 20万元

中文摘要： 精神分裂症是最严重的常见精神疾病之一，遗传因素是这一疾病最主要的风险因素，但致病基因仍然未知。最近全基因组关联分析(GWAS)数据表明：精神分裂症的遗传病因学不但包括微效多基因变异，还包括相对高致病风险的罕见拷贝数变异(CNV)。基因组上与片段复制（SDs)交叠的常见CNVs，更倾向于呈现多等位基因复杂谱式，使连锁不平衡（LD）程度较低，因而这些区域很容易被基于LD原理的关联分析所遗漏。我们建立适用于多等位基因型CNV的复杂疾病关联研究技术平台，并选择FCGR位点区域的CNV作为遗传标记，在中国汉族人群中进行病例-对照研究。然而，我们的结果表明FCGR位点4个目标区域拷贝数频率在病例组合对照组中的分布非常相似，未能发现FCGR位点CNVs和精神分裂症显著相关的证据。最近发表的一项大规模研究也表明目前可分型的常见CNV可能对复杂疾病的发病不起主要作用。尽管在这一项目中，我们最初的假设并未能得到证实，然而我们建立的基因拷贝数的定量方法却为相关研究提供了有力的工具，相关论文已被知名期刊接收。我们所收集的样品也在其它研究中得到了有效地使用。

中文关键词： 精神分裂症；拷贝数变异；片段复制；多等位基因型；关联分析

英文摘要： Schizophrenia is one of the most severe common psychiatric diseases, and genetic factors play a major aetiological role in schizophrenia. However, the susceptibility genes are still well unkown. Current data from genome-wide association studies (GWAS)imply that the genetic etiology of schizophrenia comprises common polygenic variants of small effect as well as rare copy number variants (CNVs) with larger effect. CNVs overlapping segmental duplications (SDs) are more likely to display the complex multiallelic patterns, lower linkage disequilibrium (LD) and being omited by the current GWAS.We have establish the association technical platform that is suitable for multiallelic CNVs in comlex disease, selected the CNVs in the human FCGR locus as markers, and performed a case-control study in a Chinese Han population. We found no evidence of association of target CNVs in the FCGR locus with schizophrenia. Meawhile, a recently published large scale studies concluded that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases. Although in this project, our original hypothesis was not proved, the quantitative method of gene copy established in the project provided a powerful tool for related studies,and a related paper has been accepted. Our samples were used in other genetic studies.

英文关键词： Schizophrenia; Copy number variations; Segmental duplications; Multiallelic variants; Association study