We next attempted to correlate the mean DNA methylation difference between PPD and non-PPD samples and E2-mediated DNA methylation fold change. No correlation was observed across the 1578 overlapping loci (Spearman’s ρ= −0.028, P=0.27). We refined the interrogated data set to 103 loci exhibiting nominally significant association to PPD status and observed significant correlations in both the discovery sample (Spearman’s ρ=0.21, P=0.030) and the replication sample (Spearman’s ρ=0.2, P=0.042). The P-value of association to PPD in the discovery sample was also correlated with E2 DMR effect size (Spearman’s ρ= −0.19, P=0.05) (Figure 1c), suggesting that more robust PPD associations occur at targets of larger E2-mediated DNA methylation change. Furthermore, the mean PPD minus non-PPD value was significantly correlated across the discovery and replication cohorts (Spearman’s ρ=0.32, P=0.0011) (Figure 1d). Permutation testing (20 000 iterations) demonstrated that randomly selected groupings of 103 loci did not correlate better between cohorts (P=5×10−5) nor with E2 DMR fold changes in either the discovery or replication samples (P=0.016 and 0.02, respectively). This analysis suggests that the degree to which the discovery and replication cohorts agree is strongly influenced by their localization to syntenic regions of E2-mediated epigenetic reprogramming.
