We evaluated the mean PPD minus non-PPD DNA methylation status at the nominally significant PPD associations in the prepartum depressed cohort (N=103 loci) and identified a trend for a positive correlation with the fold change at syntenic E2 DMRs (Spearman’s ρ=0.19, P=0.054). A positive correlation of mean methylation difference between the 1578 loci marked as E2 responsive was also observed between the prepartum depressed and euthymic cohorts (Spearman’s ρ=0.078, P=0.002). Cumulatively, these results support our previous hypothesis that PPD risk may be mediated by an enhanced sensitivity to E2-mediated epigenetic reprogramming.
