Recent studies have mapped regions of CTCF binding genome-wide for identification of insulator elements23, 24. One of the sites identified (OREG0020670) is a 2 kb region located 17 kb centromeric to our new T2D marker rs2334499 (Figure 2, Supplementary Figure 4). We assessed the methylation status of this CTCF binding region in DNA samples derived from peripheral blood, using bisulfite sequencing. We identified a differentially methylated region of 180 bp including seven CpG dinucleotides (Supplementary Figure 4) where the ratio of 5-methyl cytosine (Cp) varied from around 0.1-0.6. Methylation at five of the seven CpGs (CpG-1 through CpG-5) (Supplementary Figure 4), was highly correlated (Supplementary Table 9). The estimated Cp ratio was tested for correlation with SNPs in a 2 Mb surrounding region. The most significant correlation was observed between methylation status at CpG-4 and rs2334499, P = 2.6 × 10−13 (Table 2). Furthermore, correlation between rs2334499 and methylation of CpG-1 through CpG-5 was significant. For all five CpGs the T2D risk allele correlated with decreased methylation and this effect was observed regardless of whether the allele was inherited from
