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

酒精依赖中 GWAS 后全转录组 LncRNA 表达谱分析

• 批准号: 8893649
• 负责人: XINGGUANG LUO
• 金额: $ 18.82万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-10 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8893649
• 关键词: Affect; Alcohol dependence; Biological; Biological Markers; Biological Process; Brain; Cell physiology; Code; CpG Islands; Custom; Cytosine; DNA; Data; Databases; Diagnosis; Disease; Down-Regulation; Drug Targeting; Elements; Epigenetic Process; Etiology; Funding; Future; Gene Expression; Gene Expression Profile; Gene Targeting; Genetic Risk; Genetic Transcription; Genetic Variation; Genome; Genotype; Label; Liver; Messenger RNA; Methylation; Microarray Analysis; Molecular Profiling; Nature; Nervous system structure; Pathway interactions; Phenotype; Process; Proteins; Public Health; Publications; RNA; Regulation; Research; Risk; Role; Sampling; Series; Small Interfering RNA; Substance Use Disorder; System; Technology; Testing; Tissue Sample; Transcript; Untranslated RNA; Variant; base; case control; design; disorder risk; exome sequencing; genetic variant; genome wide association study; genome-wide; histone methylation; locked nucleic acid; outcome forecast; problem drinker; public health relevance; risk variant; screening; transcription factor

 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.

 描述（由应用程序提供）：全基因组关联研究（GWASS）已成功识别出酒精依赖性的显着风险变异（AD）。但是，这些风险变异与AD之间关联之间的生物学机制在很大程度上尚不清楚。长期非编码RNA（LNCRNA）（> 200nt）最近成为管理基本生物学过程的主要参与者。确定哪些LNCRNA与这些遗传风险变体相关，成为GWAS后时代的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的：1）最全面，可靠地介绍了LNCRNA在大脑中的转录组中的表达，并使用微阵列技术（n = 100）（n = 100）； 2）确定使用EQTL分析（n = 600）受基因组明显风险变异的潜在功能LNCRNA（n = 600），然后确定使用病例对照比较的AD的风险LNCRNA（n = 1200）。如果我们成功完成了这一建议，这将代表AD病因的研究中的重大进展。 LNCRNA的显着风险可能是AD诊断和预后的新重要生物标志物，并且可能是AD的新吸引力靶标。