Several explanations would be consistent with differing results between populations, such as seen at rs1881492 in CHRNG and rs2229959 in CHRNA4. First, there may be an untyped variant that is causal and has similar effects across populations, but differing correlations with typed SNPs in the two populations lead to inconsistent association evidence. Alternatively, the variant may indeed have different effects in the two populations, perhaps because of differing history and genetic background, or because of interactions with other alleles or environmental factors that occur at different rates in the populations. In that case, identifying the other background factors involved may reveal underlying common biological mechanisms. A third possibility is that the observed association may be a false positive. Potential reasons for “flip-flop” effects have been discussed by others (Lin et al., 2007, Zaykin & Shibata, 2008). Our interpretation of our “flipped” findings in CHRNG and CHRNA4 is that these regions are likely to be involved in genetic risk contributing to nicotine dependence, but further genotyping or resequencing is necessary to refine these associations. Although SNPs in this study were selected
