Post-GWAS transcriptome-wide LncRNA expression profiling in alcohol dependence

 描述(由申请人提供)：全基因组关联研究(GWAS)已经成功地确定了酒精依赖(AD)的重要风险变量。然而，这些风险变异与AD之间的联系的生物学机制在很大程度上是未知的。长的非编码RNA(LncRNAs)(&gt；200nt)最近已经成为控制基本生物过程的主要参与者。确定哪些lncRNAs与这些遗传风险变异相关，成为这个后GWAS时代合乎逻辑和必要的下一步。在这项拟议的研究中，我们有两个具体的目标：1)使用微阵列技术最全面和可靠地描述酗酒者(n=100)大脑和肝脏中跨转录组的lncRNAs的表达；2)使用eQTL分析(n=600)确定受全基因组显著AD风险变量调控的潜在功能lncRNAs，然后使用病例对照比较(n=1200)确定AD的风险lncRNAs。如果我们成功地提出了这一建议，这将代表着AD病因学研究的实质性进展。这些重要风险基因可能成为AD诊断和预后的新的重要生物标志物，并可能成为治疗AD的新的有吸引力的药物靶点。

 DESCRIPTION (provided by applicant): Genome-wide association studies (GWASs) have successfully identified significant risk variants for alcohol dependence (AD). However, the biological mechanisms underlying the associations between these risk variants and AD are largely unknown. Long non-coding RNAs (LncRNAs) (>200nt) have recently emerged as major players in governing fundamental biological processes. To determine what LncRNAs are correlated with these genetic risk variants becomes the logical and necessary next step in this post-GWAS era. In this proposed study, we have two specific aims: 1) to most comprehensively and reliably profile the expression of LncRNAs across the transcriptome in brains and livers of alcoholics (n=100) using microarray technology; 2) to identify the potential functional LncRNAs that are regulated by the genome-wide significant risk variants for AD using eQTL analysis (n=600), and then to identify the risk LncRNAs for AD using case-control comparison (n=1200). If we are successful with this proposal, this will represent substantial progress in the research o the etiology of AD. The significant risk LncRNAs could potentially be new important biomarkers for diagnosis and prognosis of AD, and may serve as new attractive drug targets for AD.