Research Paper Volume 15, Issue 14 pp 6690—6709

Figure 4. The pattern of age-associated methylation drift is determined by regional methylation level. (A) Relationship of age-linked methylation change pattern with regional methylation level. Promoters were categorized based on their methylation levels (0.1 intervals of β-values, y-axis) as indicated in different colored lines with their counts. (B) Changes in relative methylation levels in promoters with low methylation (<10%, orange) and high methylation levels (>90%, blue) as a function of age. R values indicate Pearson correlation. (C) The inverse relationship between the age-versus-methylation correlations (AMR) and the methylation levels of the regions. AMR is a Pearson correlation (R) between regional methylation levels and sample ages, with values approaching +1 and -1 indicating hyper- and hypomethylation, respectively. With the generated AMRs, the areas were grouped (0.1 intervals, totaling 20 intervals ranging from -1.0 to +1.0) and their mean methylation levels (± standard deviation) at two months of age were measured. The R² value on the plot is the determination coefficient between methylation levels and AMRs. (D) Prevalence of hypermethylation in promoters with two conflicting variables for age-associated methylation change: low CpG density (<15 ea) favoring hypomethylation, and low methylation level (<10%) favoring hypermethylation (left). Hypomethylation predominates at promoters with both low CpG density and heavy methylation (>90%, right). The regions are counted on the bar. (E) The prevalence of hypermethylation in low-methylation promoters (<10%, n = 13,076), regardless of CpG density.