There does not appear to be an effect of gender or comorbid substance dependence on the strength of the association. However, the strength of this difference varies across ethnicity and age. Specifically, despite the fact that the FTCD based definition of nicotine dependence appears to have an equivalent relationship to rs1451240 across ethnicities, the relationship between this SNP and CPD is much weaker in African Americans (β=−0.03, p=0.35), than in European Americans (β=−0.11, p=0.0005). This supports theories that nicotine dependence in African Americans is not fully captured by CPD, likely related to observations that nicotine-dependent African Americans smoke fewer CPD than European Americans(21).The equivalence of these odds ratios across ethnicities is striking especially given that the allele frequencies differ widely in the two groups. For example, the “A” allele of rs1451240 has frequencies of approximately 25% in European American controls and 70% in African American controls. The phenomenon of similar ORs across ethnicities despite different allele frequencies is considered further evidence of a true biological association(31).
