Fig. 3: Independent replication of the Bonferroni significant cross-cortex differentially methylated loci.
a The methylation (beta) effect size (ES) of the 220 cross-cortex differentially methylated positions (DMPs) identified in the discovery (N = 1408) cohorts (X-axis) were significantly correlated with the ES in the Munich replication cohort in the prefrontal cortex (red; N = 45, r = 0.64, P = 5.24 × 10−27), sorted neuronal cells (light blue; N = 26, r = 0.45, P = 1.56 × 10−12) and non-neuronal cells (purple; r = 0.79, N = 26, P = 1.43 × 10−47) (Y-axis). b A forest plot of the most significant cross-cortex DMP (cg12307200, chr3:188664632, P = 4.48 × 10−16). The effect size is shown in the prefrontal cortex (red; N = 961), temporal gyrus (green; N = 608) and entorhinal cortex (blue; N = 189) for the different discovery cohorts. The X-axis shows the beta ES, with dots representing ES and arms indicating standard error (SE). ES from the intra-tissue meta-analysis using all available individual cohorts are represented by polygons in the corresponding tissue colour. The black polygon represents the cross-cortex data. Shown in purple on the plot is the ES in the Munich replication cohort in the prefrontal cortex and sorted neuronal cells and non-neuronal cells, with the direction of effect suggesting the hypomethylation seen in the discovery cohorts is driven by changes in non-neuronal cells. c In the BDR replication cohort (N = 590) DNA methylation data were available in the prefrontal cortex for 208 of the 220 Bonferroni significant cross-cortex DMPs. The ES of these 208 cross-cortex DMPs in the discovery cohorts (X-axis) were significantly correlated with the ES in the BDR replication cohort (r = 0.53, P = 4.13 × 10−16) (Y-axis).
