D Deep sequencing of CNR1 gene network in substance dependence: Abstract This Mentored Research Career Development Award (K01) is to train Dr. Lingjun Zuo, a junior faculty member of Department of Psychiatry at Yale University, to become an independent investigator in the research field on genetics of substance dependence (SD). The trainings include three main areas: (1) advanced human molecular genetics, in particularly in """"""""Solexa"""""""" sequencing and cannabinoid receptor 1 (CNR1) gene network;(2) neuroscience, in particularly in SD, brain neural networks and functional relationship between cannabinoid receptor and protein product of other SD candidate genes;and (3) bioinformatic and statistical analytical methods for high-throughput sequence data, gene network data as well as gene x environment interaction analysis. To acquire these trainings, Dr. Zuo's time will be allocated (1) to courses and seminars, (2) to meetings with the mentor and co-mentors, (3) to interactions with other experts, and mainly (4) to the proposed research project per se. The research plan will focus on deep sequencing of CNR1 gene network that consists of CNR1 and five other biologically related genes. Dr. Zuo proposes to identify the potential functional variants underlying SD in this gene network by (1) sequencing the targeted gene regions in a relatively big size of sample using next generation sequencing approach, and by (2) using multiple-gene model to investigate the joint effects of multiple functional variants, which might exert too weak individual effects to be detectable using single-gene model. This proposed study would be promising to elucidate the genetic variants in the CNR1 gene network underlying SD, which would make a major progress in the etiology of SD, and may also be helpful to develop novel and effective treatment and prevention strategies for SD.

Public Health Relevance

Relevance to public health This proposed project will carefully study the effects of cannabinoid receptor 1 gene (CNR1) network on risk for substance dependence (SD) using the next generation deep sequencing technology, which will help us better understand the mechanism for the development of SD. The expected findings would significantly contribute to the improvement of public health.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Scientist Development Award - Research & Training (K01)
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Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Rutter, Joni
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Yale University
Schools of Medicine
New Haven
United States
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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; 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
Zuo, Lingjun; Tan, Yunlong; Wang, Zhiren et al. (2016) Long noncoding RNAs in psychiatric disorders. Psychiatr Genet 26:109-16
Zuo, Lingjun; Tan, Yunlong; Zhang, Xiangyang et al. (2015) A New Genomewide Association Meta-Analysis of Alcohol Dependence. Alcohol Clin Exp Res 39:1388-95
Wang, Ke-Sheng; Tonarelli, Silvina; Luo, Xingguang et al. (2015) Polymorphisms within ASTN2 gene are associated with age at onset of Alzheimer's disease. J Neural Transm (Vienna) 122:701-8
Zuo, Lingjun; Saba, Laura; Lin, Xiandong et al. (2015) Significant association between rare IPO11-HTR1A variants and attention deficit hyperactivity disorder in Caucasians. Am J Med Genet B Neuropsychiatr Genet 168:544-56
Zuo, Lingjun; Wang, Tong; Lin, Xiandong et al. (2015) Sex difference of autosomal alleles in populations of European and African descent. Genes Genomics 37:1007-1016
Zuo, Lingjun; Lu, Lingeng; Tan, Yunlong et al. (2014) Genome-wide association discoveries of alcohol dependence. Am J Addict 23:526-39
Zuo, Lingjun; Wang, Kesheng; Wang, Guilin et al. (2014) Common PTP4A1-PHF3-EYS variants are specific for alcohol dependence. Am J Addict 23:411-4

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