Several genome-wide association studies have linked chromosome 15q24-q25.1, a region containing the genes encoding the α3, α5, and β4 subunits of neuronal nicotinic receptors, with nicotine dependence and smoking-related illnesses such as lung cancer, airflow obstruction, and chronic obstructive pulmonary disease [1]–[6]. In candidate gene association studies, variants in the CHRNA5-A3-B4 gene cluster have been associated with nicotine dependence [7]–[14], smoking behaviors [15], [16], level of response to alcohol [17], age of initiation of drinking [15] and cocaine dependence [11], [18]. The strongest impact on the risk of substance abuse and lung cancer is associated with variation in CHRNA5.
