while 25% of individuals homozygous for the major allele are habitual smokers (Figure 1). We also performed the same analysis using rs16969968 as a covariate and confirmed that the effect of rs1996371 and correlated variants on AAO of habitual smoking is independent of the influence of rs16969968 (Table 4). The effect remained significant after controlling for other variants in this gene cluster (HR≃ 1.23, P<0.005) and Bonferroni correction for multiple testing. Some earlier studies showed that gender is a major factor influencing smoking behaviors. In our stratified analysis, although power was reduced, rs1996371 and correlated SNPs significantly predicted risk for habitual smoking with increasing age in females and males (females: rs1996371, p = 0.05, HR: 1.25; males: rs1996371, p = 0.02, HR:1.2).
