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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01DA029643-03
Application #
8284466
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Rutter, Joni
Project Start
2010-07-15
Project End
2015-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$181,818
Indirect Cost
$13,468
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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
Zuo, Lingjun; Wang, Kesheng; Luo, Xingguang (2014) Use of diplotypes - matched haplotype pairs from homologous chromosomes - in gene-disease association studies. Shanghai Arch Psychiatry 26:165-70
Zuo, Lingjun; Zhang, Heping; Malison, Robert T et al. (2013) Rare ADH variant constellations are specific for alcohol dependence. Alcohol Alcohol 48:9-14
Zuo, Lingjun; Saba, Laura; Wang, Kesheng et al. (2013) Exome-wide association study of replicable nonsynonymous variants conferring risk for alcohol dependence. J Stud Alcohol Drugs 74:622-5
Zuo, Lingjun; Wang, Ke-Sheng; Zhang, Xiang-Yang et al. (2013) Rare SERINC2 variants are specific for alcohol dependence in individuals of European descent. Pharmacogenet Genomics 23:395-402
Zuo, Lingjun; Zhang, Xiang-Yang; Wang, Fei et al. (2013) Genome-wide significant association signals in IPO11-HTR1A region specific for alcohol and nicotine codependence. Alcohol Clin Exp Res 37:730-9
Zuo, Lingjun; Wang, Kesheng; Zhang, Xiang-Yang et al. (2013) Association between common alcohol dehydrogenase gene (ADH) variants and schizophrenia and autism. Hum Genet 132:735-43
Pan, Yue; Luo, Xingguang; Liu, Xuefeng et al. (2013) Genome-wide association studies of maximum number of drinks. J Psychiatr Res 47:1717-24
Zuo, Lingjun; Wang, Kesheng; Zhang, Xiang-Yang et al. (2013) NKAIN1-SERINC2 is a functional, replicable and genome-wide significant risk gene region specific for alcohol dependence in subjects of European descent. Drug Alcohol Depend 129:254-64

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