长链非编码RNA在精神分裂症中的网络调控机制研究

Schizophrenia is a highly heritable psychiatric disorder. Associated genetic and gene expression changes have been identified by linkage and association studies, but many have not been replicated and have unknown functions. Recently, progress has been make from systematic network analysis and long non-coding RNA (lncRNA) studies. In this proposal, we aim to identify functions of lncRNA on schizophrenia. Firstly, we build up the lncRNA and mRNA co-expression network, to detect how lncRNA regulate mRNA at genome wide level. Next, we will identify the lncRNA quantitative traits loci (QTL) to explore how genetic signals regulate the expression of lncRNA. Finally, we will try to reveal regulation mechanisms of lncRNA on schizophrenia, by comparing the regulatory differences of lncRNA mRNA networks and QTLs, between patients and controls. This proposal will help us to better understanding the roles of lncRNA on molecular pathogenic mechanism of schizophrenia, and provide new targets for future drug design.

精神分裂症是一类高度遗传的精神疾病，传统的遗传连锁与关联分析发现了数以百记的易感基因，但是其中很少能够重复或者在功能试验中得到证实。近些年来，从系统水平尤其是利用网络思维分析复杂疾病取得了一定的进展。同时，也有报道长链非编码RNA（long non-coding RNA，lncRNA）在精神分裂症中发挥着重要作用。本课题拟将两者结合起来，以前期的脑组织基因表达网络分析为基础，构建lncRNA与mRNA共表达网络，以及lncRNA的数量性状遗传分析，在全基因组水平上揭示lncRNA如何受到遗传因素的调控，又是如何调控mRNA的表达，再通过精神分裂症和正常对照的调控方式的比较，阐述lncRNA在精神分裂症中所发挥的作用。本研究将有助于阐明精神分裂症的分子致病机制，以及为精神分裂症药物治疗提供新的靶点。