In a large candidate gene study by Saccone et al. (2007), variants in the putative promoter region of the CHRNB3 gene emerged as the strongest signal for association with nicotine dependence among a sample of nicotine dependent cases and non-dependent controls. Shortly thereafter, Zeiger et al. (2008), reported associations between early subjective response to tobacco and the CHRNB3/A6 genes in two samples of young adults. Analysis of individual subjective effects items revealed that “dizziness” in the period during early experimentation was a major component driving the association with SNPs in the CHRNB3 gene. The goals of this project were three-fold. First, we tested for an association between a “dizziness” phenotype among adult smokers reporting about how they felt from their first few cigarettes and 17 SNPs in the CHRNB3 promoter region (Saccone et al., in press). Second, we conducted an exploratory analysis of 209 single nucleotide polymorphisms in 15 additional CHRN genes for association with “dizziness.” Furthermore, we conducted functional analysis to examine whether different haplotypes in the CHRNB3 promoter region may lead to differential levels of gene expression.
