Fig. 3: Analysis of genomic sites showing differential enrichment for individual histone marks in subjects with a history of early-life adversity (ELA).
a Representation of three top Differential Sites (DS), identified using diffReps34. ELA is shown in red, healthy controls (C) are shown in blue. Gray rectangles delineate the coordinates of each DS. b Relative proportion of DS contributed by each histone mark. Percentages of the total number of DS, and absolute number of DS (in brackets) are shown for each mark. Both depletion- and enrichment-DS were observed for each of the six marks (Supplementary Fig. 12b). Among genes most strongly affected (Supplementary Table 5), several have been previously associated with psychopathology, such as QKI (H3K27ac top hit)40,95 or HTR1A (H3K4me3 top hit)96. c, d Top five most significant non-redundant gene ontology “Biological Processes” (c) or “Molecular Functions” (d) terms enriched for each histone mark DS, as identified by GREAT36 using hypergeometric and binomial testing (fold change ≥ 1.5 and FDR-q ≤ 0.1 for both tests). Surprisingly, the single most significant result implicated epigenetic dysregulation of odor perception in ELA subjects (consistent with recent clinical studies97), while immune processes (indicated by *), and small GTPases (+) were consistently found affected across different marks. Negative logarithmic P values are shown for binomial testing. The color indicates histone mark concerned, arrows indicate the direction of event: terms associated with depletion- (down arrow) or enrichment-DS (up arrow). Source data are provided as a Source Data file.
