Figure 4. The 175 most significant age-associated CpGs cluster together in genomic regions important for developmental, aging-related and neuronal functions. (A) A Manhattan plot of the 1696 CpG-sites with 10E-4 as cut-off value indicating the 175 most significant age-associated CpGs. (B) Circos plots of genomic locations of the 175 CpGs in CpG-islands (black), and all clock CpG-sites (blue). Insets indicate relative distributions of clock CpG-sites across genomic features. (C, D) A principal component analysis (PCA) with (C) PC1 and PC2 and (D) PC2 and PC3 based on the DNA methylation value of 175 most significant age-associated CpGs in AD (blue) and B6 (green) mouse cortex (triangles) and hippocampus (circles). Age is colored by month. N = 6. (E) The GREAT analysis associated the 175 CpGs with a regulatory domain in the mouse genome.