Fig. 4

Local CpG density affects age-associated DNA methylation trajectories. a Slope-QTL CpGs are enriched in intergenic regions. Barplot showing the % fold change observed for slope-QTL CpGs in different genome annotations versus the background of all analyzed CpGs. P-values are from 2-sided Fisher’s exact tests. b Slope-QTL CpGs are enriched in enhancer and heterochromatin states in GM12878 cells. Barplot showing the % fold change observed for slope-QTL CpGs in different chromatin states in GM12878 cells versus the background of all analyzed CpGs. Shown are significant P-values from 1-sided Fisher’s exact tests. c Slope-QTL CpGs are found in regions of low CpG density. Line plot showing the mean CpG density around slope-QTL CpGs in different window sizes. Red shows slope-QTL CpGs and black shows all other CpGs assayed. d Slope-QTL SNPs are found close to CpG sites. Histogram of the distances between slope-QTL SNPs and their nearest CpG site. Red shows the distribution for slope-QTL SNPs and gray shows all other SNPs assayed. e CpG density is a major determinant of variation in methylation trajectories with age. Boxplot showing mean methylation trajectories plotted against CpG density ± 300 bp from the CpG. The Spearman correlation, Rho, and p-value, T-test, for the association are given. For plotting, CpG density is binned into equally sized groups. Lines = median; Box = 25th–75th percentile; whiskers = 1.5 × interquartile range from box