Recent genetic meta-analyses including tens of thousands of subjects of European ancestry show strong evidence of association between smoking quantity (cigarettes per day, CPD) and multiple genetic markers on chromosome 15q25 [Liu, et al. 2010; Saccone, et al. 2010; TAG 2010; Thorgeirsson, et al. 2010]. Those studies synthesized evidence across many independent datasets to highlight specific variants in the region of the CHRNA5-CHRNA3-CHRNB4 gene cluster associated with smoking behavior in European ancestry subjects. It is important to determine the biological mechanisms underlying these associations; however, the high linkage disequilibrium (LD) in this region among individuals of European ancestry makes it difficult to differentiate potentially causal variants from the many correlated variants. Because the genetic architecture of chromosome 15q25 varies across populations, comparing associations across diverse populations with differing genetic architecture can help refine the region of association and point to variants more likely to have functional relevance [Rotimi and Jorde 2010; Saccone, et al. 2008; Zaitlen, et al. 2010].
