精神分裂症不同病双生子全基因组测序与影像遗传学研究

在精神分裂症这类多基因遗传病中，同卵双生子不同病的现象非常值得关注。精神分裂症的遗传度约为70%-80%，但目前有研究者认为，约40%-50%的精神分裂症由新发突变（de novo mutation）所引起。同卵双生子不同病患者是验证这一假说最好的研究对象。本项目拟针对已收集的8对精神分裂症不同病同卵双生子受试者及其父母进行全基因组测序，寻找可能存在的新发突变，通过生物信息学分析筛选其中与神经发育或疾病可能相关的位点进行表达分析和功能分析。同时对双生子被试进行多模态脑影像分析，进而了解患者脑网络在结构、连接和功能方面的可能缺陷，采用影像遗传学方法分析个体基因突变如何导致脑结构和功能的改变。研究结果可以检验精神分裂症新发突变假说，以及脑结构和脑功能的相应改变，并为深入理解精神分裂症的病因和分子病理机制提供基础。

Schizophrenia has been widely thought to be a polygene hereditary disease with a heritability of about 70% - 80%. However, an estimated 40% - 50% of schizophrenia is caused by de novo mutations. Monozygotic twins in which one is healthy and the other is ill represent an ideal model to validate whether de novo mutation plays a key role in the etiology of schizophrenia. We propose to investigate gene mutations and expression as well as abnormalities in brain structure and function in 8 pairs of monozygotic twins discordant for schizophrenia and their parents. Our study will focus on find new mutations in schizophrenia，and will examine function and expression of these genes affected by new mutations. We will try to identify potential defects in the brain structure and function the patients using multi-model imaging analysis. And then we will test the effects of new mutaions on brain structure and function using imging genomics analysis. Our results will test the de novo mutaion hypothesis of schizoophrenia, and may elucidate how gene mutations lead to changes in brain structure and function. Accordingly, we may also be able to uncover the possible pathogenesis, etiology and molecular pathology of schizophrenia.