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.
This proposed project will search for risk LncRNAs for alcohol dependence, which will help us better understand the biological basis of this phenotype. The expected findings will significantly contribute to the improvement of public health.
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