Moreover, human genetic association studies have indicated that the minor allele of rs16969968 in CHRNA5, encoding a single nucleotide polymorphism in the α5 subunit of the nAChR, to be associated with increased risk of nicotine dependence [21,56] and association with the level of alcohol response to an alcohol challenge and dependence [20,23]. Here, CHRNA5 is linked to substance dependence.