rs1329650 on 10q25 (β = 0.367, SE = 0.059, p-value = 5.7 × 10−10), and rs3733829 in 9p13 of EGLN2 (β = 0.333, SE = 0.058, p-value = 1.0 × 10−8) and number of cigarettes per day, and rs3025343 near DBH on chromosome 9 and smoking cessation (OR = 1.12, 95%CI: 1.08–1.18, p-value = 3.6 × 10−8) (11). Still, the variance attributed to these genetic variants only explains a small proportion of phenotypic variation in cigarette use, which does not correspond to estimates of heritability calculated from twin and family studies. A portion of this “missing heritability” might be explained by gene-environment interaction (42), emphasizing the importance of studying GxE. Although reliable demonstration of GxE requires very large sample sizes, studies of GxE can be helpful in determining why heritability estimates for cigarette use phenotypes vary, and could explain why the search for susceptibility genes from GWAS have not been especially successful. Identified genetic loci from the current literature contribute only modestly to the variability in cigarette use phenotypes. Once we are able to identify more genes contributing to cigarette use, studies of GxE could be used to shape smoking cessation therapies and tobacco control efforts, through interventions tailored to
