title: Association of CHRNA4 polymorphisms with smoking behavior in two populations.
abstract: CHRNA4, the gene that encodes the nicotinic acetylcholine receptor α(4) subunit, is a potential candidate gene for nicotine dependence (ND). However, studies of the association of CHNRA4 with smoking behavior have shown inconsistent results. Our meta-analysis of linkage studies of smoking behavior identified a genome-wide significant linkage of the phenotype maximum number of cigarettes smoked in a 24-hour period to a region (20q13.12-q13.32) harboring CHRNA4. This motivated us to examine the association of CHRNA4 with smoking behavior in two independent samples. In this study, we examined five single nucleotide polymorphisms (SNPs) within CHRNA4 and three smoking-related behaviors: one quantitative trait [cigarettes smoked per day (CPD)], and two binary traits [DSM-IV diagnosis of ND and dichotomized Fagerstrom test of ND (FTND)], in 1,249 unrelated European-Americans (EAs) and 1,790 unrelated African-Americans (AAs). Using the combined sample with sex, age, and race as covariates, the synonymous SNP rs1044394 was significantly associated with ND (P = 0.001) and FTND (P = 0.01). Rs2236196, which has a low correlation with rs1044394, was also significantly associated with CPD (P = 0.003). The pattern of association for these SNPs was similar in AAs and EAs. After correction for multiple testing, the association between rs1044394 and ND in the combined sample remained significant (P = 0.033). In summary, our study supports association between CHRNA4 common variation and ND in AA and EA samples. Additional studies will be necessary to evaluate the role of rare variants at CHRNA4 for ND.
authors: Department of Psychiatry, Division of Human Genetics, Yale University School of Medicine, New Haven, Connecticut, USA.
authors: Shizhong
authors: S
authors: Han
authors: Bao-Zhu
authors: BZ
authors: Yang
authors: Henry R
authors: HR
authors: Kranzler
authors: David
authors: D
authors: Oslin
authors: Raymond
authors: R
authors: Anton
authors: Joel
authors: J
authors: Gelernter
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000208:ethnology / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000208:ethnology / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D011978:Receptors, Nicotinic