In summary, rs16969968 represents a risk locus for nicotine dependence in African-Americans as well as in European-Americans. We have evidence of a potentially complex role for gene-expression-associated SNPs such as rs555018 and rs588765 in the two populations. The “protective” association at rs578776 and its correlates is seen in European-Americans but not in African-Americans. Less common variants such as the novel SNP in the CHRNA5-CHRNA3 overlapping region also are associated with risk. Overall, multiple variants in this gene cluster are contributing to nicotine dependence risk and therefore to risk for diseases for which smoking is a major contributing factor.
