As shown in Table 2, there were seven other genes or regions at which significant probes were identified in the literature reviewed. In general, delta beta values for these regions and probes were less than that of AHRR/cg05575921, making them less ideal as potential biomarkers. At some loci, such as 2q37.1 CpGs cg05951221, cg2156664, and cg01940273, average delta beta values in the studies reviewed were in approximately the 10%–15% range, indicating some potential as adjunctive biomarkers, however. However, in the study of Philibert and colleagues [72], multi-marker models including all three of these CpGs, as well as AHRR CpGs cg05575921 and cg23576855, did not improve the AUC in receiver operating characteristic (ROC) analyses. In addition, at other loci such as 6p21.33 CpG cg06126421, at least one study reported a delta beta value as high as 23% [28], but this magnitude has not been replicated in other studies. Interestingly, the same CpG was among the top two most associated with all-cause, cardiovascular, and cancer mortality in on recent study, although the delta beta for the CpG was only 13% (current versus never smokers) [59].
