that are present in this region, which may be associated with different functions, and perhaps slightly different endophenotypes (Saccone et al. 2009a, b; Saccone et al. 2010). SNP rs1051730, present on many of the GWA platforms, is in near perfect linkage disequilibrium (LD, as measured by r2) with rs16969968, and has emerged from several GWA studies of nicotine behaviors and lung cancer (Amos et al. 2008; Thorgeirsson et al. 2008, 2010). It has also been examined in meta-analyses where association with tobacco behaviors reaches genome-wide significance levels for two independent loci (Saccone et al. 2010; Thorgeirsson et al. 2010). More recently, SNPs in this region have been associated with externalizing behaviors, supporting a more general role of these genes that is not specific to nicotine (Stephens et al. 2011). Our aim is to extend these findings by focusing on a more fine-grained definition of different substance initiation phenotypes and their relative association with specific genetic signals in the CHRNA5/A3/B4 gene cluster.
