This study also has limitations. The positive linkage finding by genome scan meta-analysis in our previous study is consistent with a role for multiple rare (or less common) variants mapped to this region for ND; however, these were not investigated in present study. Further, there is evidence that the rare missense variants at CHRNA4 are associated with sporadic amyotrophic lateral sclerosis (Sabatelli et al., 2009). The role of rare variants at this locus for ND and related behaviors thus needs to be evaluated. With increasing evidence for a role of rare variants in psychiatric disorders (Carroll et al., 2010; Knight et al., 2009), we believe that sequencing the whole gene will be necessary to discover all of the causal variants in CHNRA4, especially rare variants, that are associated with smoking behavior. In addition, the AA and EA samples differed significantly on MAF for the five SNPs. There is a possibility that adjustment for self-reported race in the combined analysis may not be sufficient to address this confounding by race. However, in a subgroup of samples with AIMs available, the association
