First, this study extends the finding of genetic association with nicotine dependence into an African American population. Thus far, the majority of genetic studies, including those of substance dependence, have been conducted using European ancestry samples (18). Our findings indicate that the A allele of rs13273442 is associated with protection from nicotine dependence in African American subjects as well as European American subjects. This allele, which is common in both populations, displays a consistent protective effect across all three of our African American samples and represents a similar strong decrease in risk for each copy of the A allele carried in both ancestral populations (OR=0.80 for African Americans; OR=0.75 for European Americans). Meta-analyzing the European Ancestry and African American datasets strengthened the statistical evidence for association, resulting in a p-value of 8.6 × 105 and further increasing confidence in the validity of this genetic finding. This conclusion is supported by a recent study of nicotine dependence that focused on this region (19) and reported significant association for rs6474412, a correlate of rs13273442 (r2 ≥ 0.89) in three populations: European-American, African-American, and Asian.