The main human genetic evidence comes from studies investigating nicotine dependence (ND) or ND related phenotypes including first use of tobacco. Some evidence has been reported also for alcohol initiation (Schlaepfer et al. 2008), alcohol dependence (Chen et al. 2009; Sherva et al. 2010), level of response to alcohol and other substance use. Converging evidence has been established for rs16969968 in the CHRNA5 gene. This non-synonymous SNP has been associated with ND (Saccone et al. 2009a), ND severity/heavy smoking (Weiss et al. 2008, Stevens et al. 2008), habitual smoking (Bierut et al. 2008) and early onset of smoking (Weiss et al. 2008). It has also been shown to affect receptor function, where the risk allele was associated with decreased response to a nicotine agonist (Bierut et al. 2008). Several recent papers have begun to disentangle the multiple distinct genetic signals 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
