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Open AccessArticle

Replicated Risk Nicotinic Cholinergic Receptor Genes for Nicotine Dependence

Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA
Curriculum & Research Support Department, Cushing/Whitney Medical Library, Yale University School of Medicine, New Haven, CT 06510, USA
Shanghai Mental Health Center, Shanghai 200030, China
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510, USA
Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Biological Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing 100096, China
Department of Neurology, Shanghai First People’s Hospital, Shanghai Jiao Tong University, Shanghai 200080, China
Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Diseases of Tibet Autonomous Region, Xizang Minzu University School of Medicine, Xianyang, Shanxi 712082, China
Provincial Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong 226001, China
Departments of Genetics, Genomics, Informatics, Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Nevada Institute of Personalized Medicine, University of Nevada, Las Vegas, NV 89154, USA
Department of Psychology, University of Nevada, Las Vegas, NV 89154, USA
Authors to whom correspondence should be addressed.
Academic Editor: Paolo Cinelli
Genes 2016, 7(11), 95;
Received: 4 July 2016 / Revised: 20 October 2016 / Accepted: 2 November 2016 / Published: 7 November 2016
(This article belongs to the Special Issue Genetic Mechanism of Psychiatric Disorders)
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. View Full-Text
Keywords: CHRN; nAChR; nicotine dependence; replication; bioinformatics CHRN; nAChR; nicotine dependence; replication; bioinformatics
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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.-S.R.; Luo, X. Replicated Risk Nicotinic Cholinergic Receptor Genes for Nicotine Dependence. Genes 2016, 7, 95.

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