Replicated Risk Nicotinic Cholinergic Receptor Genes for Nicotine Dependence.
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 usingcis-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-B4andCHRNA4). 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 betweenCHRNB3-A6,CHRNA5-A3-B4,CHRNA4and ND/CPD are very robust. More research is needed to examine how these genetic variants contribute to the risk for ND/CPD.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA. Lingjun.Zuo@yale.edu.
Lingjun
L
Zuo
Curriculum & Research Support Department, Cushing/Whitney Medical Library, Yale University School of Medicine, New Haven, CT 06510, USA. Rolando.Milian@yale.edu.
Rolando
R
Garcia-Milian
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA. Xiaoyun.Guo@yale.edu.|Shanghai Mental Health Center, Shanghai 200030, China. Xiaoyun.Guo@yale.edu.|Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510, USA. Xiaoyun.Guo@yale.edu.
Xiaoyun
X
Guo
Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China. chunlongzhong@126.com.
Chunlong
C
Zhong
Biological Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing 100096, China. yltan21@126.com.
Yunlong
Y
Tan
Biological Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing 100096, China. zhiren75@163.com.
Zhiren
Z
Wang
Shanghai Mental Health Center, Shanghai 200030, China. jijunwang27@163.com.
Jijun
J
Wang
Department of Neurology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai 200080, China. x_p_wang@sjtu.edu.cn.
Xiaoping
X
Wang
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. klonglister@gmail.com.
Longli
L
Kang
Provincial Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong 226001, China. lulu@uthsc.edu.|Departments of Genetics, Genomics, Informatics, Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA. lulu@uthsc.edu.
Lu
L
Lu
Nevada Institute of Personalized Medicine, University of Nevada, Las Vegas, NV 89154, USA. xiangning.chen@unlv.edu.|Department of Psychology, University of Nevada, Las Vegas, NV 89154, USA. xiangning.chen@unlv.edu.
Xiangning
X
Chen
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA. Chiang-Shan.Li@yale.edu.
Chiang-Shan R
CR
Li
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA. Xingguang.Luo@yale.edu.|Biological Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing 100096, China. Xingguang.Luo@yale.edu.
Xingguang
X
Luo
CHRN; bioinformatics; nAChR; nicotine dependence; replication