Table III presents the joint genotype analysis. From the allele frequencies in Table II (column 7), we see that rs16969968 represents a locus whose minor allele (A) confers risk for addiction, while rs578776 represents a locus whose minor allele (A) is protective. Thus, as expected, the GG/AA genotype combination for rs16969968/rs578776 confers the greatest protection from nicotine dependence, while the AA/GG is associated with the highest risk (Table III). The odds of nicotine dependence relative to non-dependence among those with the highest risk joint genotype is 2.5 higher than in those with the lowest risk. It is interesting to note the zero cells for the AG/AA, AA/AG and AA/AA combinations, which clarifies that the high risk genotype AA at rs16969968 occurs only in combination with the homozygous “risk” GG genotype at rs578776. We thus cannot observe the effect of the AA genotype at rs16969968 on other background genotypes at rs578776, and similarly the A-A haplotype is not observed (double heterozygotes being extremely likely to carry A-G and G-A). However, the effect on the observed background is clear from the cells
