Though the genetics of substance dependence are complex, recent studies have successfully identified several genes that contribute to the development of nicotine dependence. The region of chromosome 8p11 that includes the α6 –β3 nicotinic receptor subunit gene cluster has been associated with smoking behavior (1–7). A set of common, highly correlated variants (r2=1.0) tagged by rs13273442, rs6474412, and rs1451240 is associated with smoking behaviors at genome-wide significance in European ancestry populations: for the quantitative smoking phenotype “cigarettes per day” (p = 1.3 × 10−8 using rs6474412 (1)) and for dependence using a case-control phenotype based on the Fagerström Test for Nicotine Dependence (8) (p = 2.4 × 10−8 using rs1451240 (7)). When robust evidence is discovered that a genetic variant contributes to dependence on a particular substance, three questions logically arise: (1) Is the identified association robust across different ancestral populations? (2) Is the association specific to a single substance, or does it represent a general substance dependence risk? (3) Are there additional, statistically independent genetic associations in the region?
