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

基本信息

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
项目类别：
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

项目摘要

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（由申请人提供）：全基因组关联研究（GWASS）成功地识别了酒精依赖性的显着风险（AD），但是，这些风险变异和AD之间的关联的生物学机制在很大程度上是未知的RNA（lncrnas）（> 200nt）最近出现了基本生物过程的主要参与者。 1）使用微阵列技术的大多数综合性和lncross累计的表达（n = 100）； = 600），并使用控制比较来识别AD的风险（n = 1200）。 AD Y的程序可以充当AD的新有吸引力的药物目标。