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

Authors

L Zuo, Yale University School of MedicineFollow
Y Tan, Beijing Huilongguan HospitalFollow
C S.R. Li, Yale University School of MedicineFollow
Z Wang, Beijing Huilongguan HospitalFollow
K Wang, East Tennessee State UniversityFollow
X Zhang, University of Texas Health Science Center at HoustonFollow
X Lin, Fujian Provincial Cancer Hospital
X Chen, University of Nevada, Las VegasFollow
C Zhong, Shanghai Jiao Tong UniversityFollow
X Wang, Shanghai Jiao Tong University
J Wang, Shanghai Mental Health CenterFollow
L Lu, University of Tennessee Health Science CenterFollow
X Luo, Yale University School of MedicineFollow

Document Type

Article

Publication Date

1-1-2016

Publication Title

American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

Volume

171

Issue

8

First page number:

1057

Last page number:

1071

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. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Keywords

alcohol dependence; CHRN; mRNA expression; nAChR; nicotine dependence; rare variant

Language

English

Repository Citation

Zuo, L., Tan, Y., Li, C. S., 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, 171(8), 1057-1071.
http://dx.doi.org/10.1002/ajmg.b.32476