The non-synonymous SNP, rs16969968 was not associated with age at onset of daily smoking. We further wanted to explore whether daily smokers with these variants are at increased risk of becoming habitual smokers in future. Our Cox-proportional hazard analysis indeed showed that smokers who have an early AAO of daily smoking and carry a minor allele of rs1996371 have approximately 1.2 times higher risk of becoming habitual smokers compared to daily smokers who carry the major allele. This association was further confirmed in stratified analysis in EAs (rs1996371, p = 0.03, HR: 1.17). In African Americans the variant was not statistically significant, most likely because of low power, but the effect was in the same direction (rs1996371, p>0.05, HR: 1.21). SNP rs1996371 has low correlation (0.28<r2<0.56 in Europeans using HapMap data, Figure 2) with variants (e.g. rs1051730, rs16969968) that were reported to affect risk for nicotine dependence and smoking related diseases in adults. Interestingly Schlaepfer et al reported a variant in the 3′UTR of CHRNB4 gene, rs1948, has been linked to early age of initiation for tobacco use in an ethnically diverse young adult cohort [32]. They also found that a variant, rs11634351 that is in low LD with rs1948
