Because these variants occurred in only a limited number of individuals, we used a collapsing burden test to assess their cumulative effect after adjusting for the effect of rs16969968 and low frequency variants. Overall, 37 individuals possessed at least 1 rare variant (details of these individuals in Supplemental Table S6). In the primary sample, the aggregate rare variant term was associated with a risk effect in the European Americans (OR=12.9, p=0.01) as 12/13 (92%) individuals with at least one rare variant were nicotine dependent cases (Table 2, Table S6). In African Americans, the rare variant term was in the same risk direction but not significant (OR=1.5, p=0.37) as 17/24 (71%) of the individuals with at least one rare variant were nicotine dependent cases.
