We also examined this locus to see if the association signal was represented by one variant or if there were potentially multiple distinct variants associated with nicotine dependence. The variant rs4952 was the focus of this investigation, and we chose it because of its low correlation to rs13273442 in both ancestral populations (r2=0.10, in European Americans, r2<0.001 in African Americans) and a previous report of association to nicotine dependence (6). We recognized that the power of this analysis would be decreased due to the low frequency of the T allele for rs4952 (European Americans (3.0%) and African Americans (0.8%)). In spite of the modest power, tests of association between rs4952 and nicotine dependence conditioned on the common variant rs13273442 resulted in point estimates indicating a protective effect for the minor allele in both groups (OR=0.75 for European Americans, OR=0.59 for African Americans). Meta-analysis across the two ancestral groups tightened the confidence interval enough that the result is statistically significant (OR=0.72; p=0.02). We thus believe that multiple variants in this region contribute to the genetic risk for nicotine dependence.
