title: Associations of rare nicotinic cholinergic receptor gene variants to nicotine and alcohol dependence.
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.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Zuo
authors.affiliation: Biological Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing, China.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Chiang-Shan R
authors.initials: CR
authors.lastname: Li
authors.affiliation: Biological Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing, China.
authors.forename: Zhiren
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, Tennessee.
authors.forename: Kesheng
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Provincial Key Laboratory of Translational Cancer Medicine, Fujian Provincial Cancer Hospital, Fuzhou, Fujian, China.
authors.forename: Xiandong
authors.initials: X
authors.lastname: Lin
authors.affiliation: Nevada Institute of Personalized Medicine and Department of Psychology, University of Nevada, Las Vegas, Nevada.
authors.forename: Xiangning
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Chunlong
authors.initials: C
authors.lastname: Zhong
authors.affiliation: Department of Neurology, Shanghai First People's Hospital, Shanghai Jiao-Tong University, Shanghai, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of EEG and Neuroimaging, Shanghai Mental Health Center, Shanghai, China.
authors.forename: Jijun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Provincial Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, China.|Departments of Genetics, Genomics, Informatics, Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.|Biological Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing, China.
authors.forename: Xingguang
authors.initials: X
authors.lastname: Luo
mesh_terms: D001741:Black or African American / Q000235:genetics; D000437:Alcoholism / Q000235:genetics*; D000818:Animals; D016022:Case-Control Studies; D030561:Databases, Nucleic Acid; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008297:Male; D051379:Mice; D009538:Nicotine / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D011978:Receptors, Nicotinic; D009538:Nicotine
keywords: CHRN; alcohol dependence; mRNA expression; nAChR; nicotine dependence; rare variant