in the joint analysis, with a reversal of the direction of effect for locus 3. This evidence of statistically independent association for locus 3 with smoking in our analysis is compelling given that these SNPs have also been implicated in altered mRNA levels for CHRNA5 in brain and lung tissue from European-ancestry subjects [21], [22], [24]. Thus, both statistical and functional evidence indicate that at least one SNP correlated with CHRNA5 mRNA levels is involved in risk, and highlight locus 3 as an important group of SNPs for further investigation.