CEU [Abecasis et al., 2012]. A second study targeting age of tobacco initiation in a Korean sample found that SNPs rs6495308, rs11072768, and rs951266 were significant for association [Li et al., 2010], but it is not clear whether in this sample these SNPs are in high linkage disequilibrium with the four previously described loci. Two genome-wide meta-analyses (with CPD as the primary phenotype) also included age of tobacco initiation as an outcome and did not find any association that exceeded genome-wide significance [Furberg et al., 2010; Thorgeirsson et al., 2010]. In another large meta-analysis, age at onset of regular smoking modified the association between rs16969968 and CPD, with early onset of smoking being associated with a stronger gene–phenotype association. In that analysis, no association was seen between dichotomized age of onset (at age 16) and rs16969968 (P = 0.77) among 67,128 smokers [Hartz et al., 2012]. Thus, while some reports have found evidence for association in this region with age of tobacco initiation, others have not, and it has not been clear whether separate independent loci in these genes may be associated with different phenotypes related to early smoking behavior.
