Abstract

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.

Public Health Relevance

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AA023237-02
Application #
9142274
Study Section
Neuroscience Review Subcommittee (AA)
Program Officer
Reilly, Matthew
Project Start
2015-09-10
Project End
2017-08-31
Budget Start
2016-09-01
Budget End
2017-08-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost

  Institution

Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code

  Publications

Chen, Yang; Xu, Chun; Harirforoosh, Sam et al. (2018) Analysis of PTPRK polymorphisms in association with risk and age at onset of Alzheimer's disease, cancer risk, and cholesterol. J Psychiatr Res 96:65-72
Wang, Kesheng; Liu, Ying; Ouedraogo, Youssoufou et al. (2018) Principal component analysis of early alcohol, drug and tobacco use with major depressive disorder in US adults. J Psychiatr Res 100:113-120
Wang, Ke-Sheng; Liu, Ying; Xu, Chun et al. (2017) Family-based association analysis of NAV2 gene with the risk and age at onset of Alzheimer's disease. J Neuroimmunol 310:60-65
Wang, Ke-Sheng; Liu, Ying; Gong, Shaoqing et al. (2017) Bayesian Cox Proportional Hazards Model in Survival Analysis of HACE1 Gene with Age at Onset of Alzheimer's Disease. Int J Clin Biostat Biom 3:
Guo, Xiaoyun; Qiu, Wenying; Garcia-Milian, Rolando et al. (2017) Genome-wide significant, replicated and functional risk variants for Alzheimer's disease. J Neural Transm (Vienna) 124:1455-1471
Qiu, Wenying; Guo, Xiaoyun; Lin, Xiandong et al. (2017) Transcriptome-wide piRNA profiling in human brains of Alzheimer's disease. Neurobiol Aging 57:170-177
Zuo, Lingjun; Tan, Yunlong; Wang, Zhiren et al. (2016) Long noncoding RNAs in psychiatric disorders. Psychiatr Genet 26:109-16
Zuo, Lingjun; Tan, Yunlong; Li, Chiang-Shan R et al. (2016) Associations of rare nicotinic cholinergic receptor gene variants to nicotine and alcohol dependence. Am J Med Genet B Neuropsychiatr Genet 171:1057-1071
Zuo, Lingjun; Wang, Zhiren; Tan, Yunlong et al. (2016) piRNAs and Their Functions in the Brain. Int J Hum Genet 16:53-60
Cao, Yuping; Shen, Jingjin; Li, Wen et al. (2016) The symptom trajectories to clinical remission in Chinese patients with unipolar major depressive disorder. Asia Pac Psychiatry 8:309-311

Showing the most recent 10 out of 15 publications