Because the risk and protective SNPs represent two separate associations, the combined influence of the variants was assessed to determine how heavy smoking was affected by genotype combinations of SNPs from each group. The nonsynonymous SNP rs16969968 was used to represent the risk group and rs3743078, one of the most significantly associated SNPs, was used to represent the protective group. The combination of the wild-type genotype of rs16969968 (GG) and homozygous variant genotype of rs3743078 (GG) is associated with the lowest risk for heavy smoking (Table 4, shaded cell) whereas the AA/CC genotype combination is associated with the highest risk (Table 4, outlined cell). The odds of heavy smoking relative to light smoking among smokers with the highest risk genotype combination was 2.43 times higher than in those with the lowest risk genotype combination.
