Associations of rare nicotinic cholinergic receptor gene variants to nicotine and alcohol dependence

Lingjun Zuo, Yunlong Tan, Chiang Shan R. Li, Zhiren Wang, Kesheng Wang, Xiangyang Zhang, Xiandong Lin, Xiangning Chen, Chunlong Zhong, Xiaoping Wang, Jijun Wang, Lu Lu, Xingguang Luo

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Nicotine's rewarding effects are mediated through distinct subunits of nAChRs, encoded by different nicotinic cholinergic receptor (CHRN) genes and expressed in discrete regions in the brain. In the present study, we aimed to test the associations between rare variants at CHRN genes and nicotine dependence (ND), and alcohol dependence (AD). A total of 26,498 subjects with nine different neuropsychiatric disorders in 15 independent cohorts, which were genotyped on Illumina, Affymetrix, or PERLEGEN microarray platforms, were analyzed. Associations between rare variants (minor allele frequency (MAF) <0.05) at CHRN genes and nicotine dependence, and alcohol dependence were tested. The mRNA expression of all Chrn genes in whole mouse brain and 10 specific brain areas was investigated. All CHRN genes except the muscle-type CHRNB1, including eight genomic regions containing 11 neuronal CHRN genes and three genomic regions containing four muscle-type CHRN genes, were significantly associated with ND, and/or AD. All of these genes were expressed in the mouse brain. We conclude that CHRNs are associated with ND (mainly) and AD, supporting the hypothesis that the full catalog of ND/AD risk genes may contain most neuronal nAChRs-encoding genes.

Original languageEnglish (US)
Pages (from-to)1057-1071
Number of pages15
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume171
Issue number8
DOIs
StatePublished - Dec 1 2016

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Tobacco Use Disorder
Nicotinic Receptors
Cholinergic Receptors
Alcoholism
Genes
Brain
Muscles
Nicotine
Gene Frequency

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Associations of rare nicotinic cholinergic receptor gene variants to nicotine and alcohol dependence. / Zuo, Lingjun; Tan, Yunlong; Li, Chiang Shan R.; Wang, Zhiren; Wang, Kesheng; Zhang, Xiangyang; Lin, Xiandong; Chen, Xiangning; Zhong, Chunlong; Wang, Xiaoping; Wang, Jijun; Lu, Lu; Luo, Xingguang.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 171, No. 8, 01.12.2016, p. 1057-1071.

Research output: Contribution to journalArticle

Zuo, L, Tan, Y, Li, CSR, Wang, Z, Wang, K, Zhang, X, Lin, X, Chen, X, Zhong, C, Wang, X, Wang, J, Lu, L & Luo, X 2016, 'Associations of rare nicotinic cholinergic receptor gene variants to nicotine and alcohol dependence', American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 171, no. 8, pp. 1057-1071. https://doi.org/10.1002/ajmg.b.32476
Zuo, Lingjun ; Tan, Yunlong ; Li, Chiang Shan R. ; Wang, Zhiren ; Wang, Kesheng ; Zhang, Xiangyang ; Lin, Xiandong ; Chen, Xiangning ; Zhong, Chunlong ; Wang, Xiaoping ; Wang, Jijun ; Lu, Lu ; Luo, Xingguang. / Associations of rare nicotinic cholinergic receptor gene variants to nicotine and alcohol dependence. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2016 ; Vol. 171, No. 8. pp. 1057-1071.
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