Document Type
Article
Publication Date
11-7-2016
Publication Title
Genes
Volume
7
Issue
11
First page number:
1
Last page number:
20
Abstract
It has been hypothesized that the nicotinic acetylcholine receptors (nAChRs) play important roles in nicotine dependence (ND) and influence the number of cigarettes smoked per day (CPD) in smokers. We compiled the associations between nicotinic cholinergic receptor genes (CHRNs) and ND/CPD that were replicated across different studies, reviewed the expression of these risk genes in human/mouse brains, and verified their expression using independent samples of both human and mouse brains. The potential functions of the replicated risk variants were examined using cis-eQTL analysis or predicted using a series of bioinformatics analyses. We found replicated and significant associations for ND/CPD at 19 SNPs in six genes in three genomic regions (CHRNB3-A6, CHRNA5-A3-B4 and CHRNA4). These six risk genes are expressed in at least 18 distinct areas of the human/mouse brain, with verification in our independent human and mouse brain samples. The risk variants might influence the transcription, expression and splicing of the risk genes, alter RNA secondary or protein structure. We conclude that the replicated associations between CHRNB3-A6, CHRNA5-A3-B4, CHRNA4 and ND/CPD are very robust. More research is needed to examine how these genetic variants contribute to the risk for ND/CPD. © 2016 by the authors; licensee MDPI, Basel, Switzerland.
Keywords
Bioinformatics; CHRN; NAChR; Nicotine dependence; Replication
Disciplines
Life Sciences
File Format
File Size
978
Language
English
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Repository Citation
Zuo, L.,
Garcia-Milian, R.,
Guo, X.,
Zhong, C.,
Tan, Y.,
Wang, Z.,
Wang, J.,
Wang, X.,
Kang, L.,
Lu, L.,
Chen, X.,
Li, C. R.,
Luo, X.
(2016).
Replicated Risk Nicotinic Cholinergic Receptor Genes for Nicotine Dependence.
Genes, 7(11),
1-20.
http://dx.doi.org/10.3390/genes7110095