T cells, B cells and granulocytes, and observed a significant association with prepartum depression status (cell ratio, depressed=0.021±5.2×10−4, euthymic=0.032±3.3×10−4, P=2.1×10−4) but not PPD status (cell ratio, PPD=0.028±5×10−4, non-PPD=0.028±4.2×10−4, P=0.86) (Figure 3a), the distribution of which was similar but opposite to that of HP1BP3 DNA methylation (Figure 3b). This monocyte to non-monocyte cell-type ratio was negatively correlated with DNA methylation of HP1BP3 (Spearman’s ρ= −0.37, P=0.0074) (Figure 3c), whereas TTC9B was not associated (Spearman’s ρ= −0.22, P=0.11). Linear regression modeling was performed for PPD diagnosis against an interaction of HP1BP3 DNA methylation with the cell-type ratio, With TTC9B DNA methylation as a covariate. The model was significantly associated with PPD (R2=0.38, P=1.9×10−4), as were all model terms including DNA methylation of HP1BP3 (β= −0.22±0.075, P=0.0044), TTC9B (β= −0.033±0.0081, P=1.6×10−4), the cell-type ratio (β= −49.66±14.64, P=0.0014), and the interaction between HP1BP3 DNA methylation and cell-type ratio (β=8.03±2.4, P=0.0016). Using a bootstrapping method, we predicted PPD status for each individual using the linear model and obtained an AUC of 0.82 (Figure 3d).
