title: Genetic association of the CHRNA6 and CHRNB3 genes with tobacco dependence in a nationally representative sample.
abstract: Neuronal nicotinic acetylcholine receptors are activated by both endogenous acetylcholine and exogenous nicotine, making sequence variations in these receptors likely candidates for association with tobacco phenotypes. Previous studies have found evidence for significant association between single nucleotide polymorphisms (SNPs) in the genomic region containing the CHRNA6 and CHRNB3 genes and tobacco behaviors. In this study, we provide support for an association between these genes and tobacco dependence in the National Youth Survey Family Study wave 10, a nationally representative sample of households. Eight SNPs in the CHRNA6 and CHRNB3 genomic region were genotyped in 1051 subjects, approximately half of whom are members of sibling pairs. Genetic association with DSM-IV dependence was assessed using a family-based approach as implemented in the statistical package PBAT. Individual SNPs were tested for association with quit attempts and overall dependence. Variation in CHRNA6 was found to be associated with tobacco dependence (p=0.007 in Caucasians). SNPs in CHRNB3 were found to be associated with the number of quit attempts (p=0.0024). Together these results further implicate the region downstream of CHRNA6 and the region upstream of CHRNB3 in risk of nicotine dependence.
authors.affiliation: Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Hoft
authors.forename: Robin P
authors.initials: RP
authors.lastname: Corley
authors.forename: Matthew B
authors.initials: MB
authors.lastname: McQueen
authors.forename: Isabel R
authors.initials: IR
authors.lastname: Schlaepfer
authors.forename: David
authors.initials: D
authors.lastname: Huizinga
authors.forename: Marissa A
authors.initials: MA
authors.lastname: Ehringer
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003625:Data Collection; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics*; D035781:Siblings; D016540:Smoking Cessation; D014029:Tobacco Use Disorder / Q000235:genetics*; D014481:United States
chemical_list: C470410:CHRNA6 protein, human; C539371:CHRNB3 protein, human; D011978:Receptors, Nicotinic