In the body, the opening of these channels is controlled by the endogenous ligand, acetylcholine, a chemical produced by neurons to activate other nearby neurons. Nicotine, the major psychoactive chemical present in tobacco smoke is a chemical present in the environment that can also stimulate the opening of these nicotinic acetylcholine receptor ion channels [9]. A number of GWAS studies have been performed that demonstrate an association between the nicotinic receptors and smoking. The strongest association between nicotinic receptors and nicotine addiction is a non-synonymous change (rs16969968, D398N) in the gene encoding the α5 subunit of the nicotinic receptor (CHRNA5) on chromosome 15 [7,10–14]. When cells are made to express nicotinic receptors containing the minor allele form of this SNP (398N), agonists induce less channel opening and cell activation than in cells that express receptors containing the major allele (398D) [11]. Thus, the minor allele at this SNP results in a significant functional change in the behavior of this ion channel, causing more nicotine to be needed in individuals with the minor allele to produce the same effect. Additionally, SNPs
