Unfortunately, the association has not replicated in studies using non-adult age groups (including prenatal exposure), or tissues other than peripheral blood cells. This lack of generalizability represents a limitation when compared to the AHRR locus, as will be discussed below. Another limitation is that the maximum magnitude of the finding (absolute difference in average methylation level or delta beta) is reported to be in the range of 8% to 10%, which may limit its detection in smaller studies. Finally, none of the studies finding the association performed genotype by methylation (GxMeth) analyses to avoid confounding of findings by genotype. This is an important consideration because according to dbSNP, the CpG residue interrogated by cg03636183 is 46 bp from rs773902, a SNP which is in marked population disequilibrium [56].
