Unrelated individuals who could not be included in the PBAT analyses were used to confirm the results. These singletons were examined for genetic association of SNPs with quit attempts and with overall dependence, using simple Chi Square and ANOVA analysis in SPSS. The left -most two columns of Table 7 show the results of these analyses in the current frequent smokers. rs7004381, rs4950, and rs13280604 in CHRNB3 were found to be associated with overall nicotine dependence using a recessive model (p=0.039, p=0.007, p=0.006), with corresponding odds ratios of: 3.36 (1.01 –11.11) for rs7004381, 4.62 (1.44 – 14.84) for rs4950, and 4.67 (1.46 – 14.95) for rs13280604. Fisher’s method was used to combine the p-values from the above-described PBAT sibpairs analysis with the results from the singletons, shown in the second set of columns in Table 7 (Combined). In addition to boosting the significance of the CHRNB3 SNP rs4950 to p=0.022, rs2304297 in CHRNA6 was also nominally associated with tobacco dependence (p=0.023). Results of analysis of all subjects are shown in the right half of Table 7. In the singletons, there