Figure 1. Discovery and validation strategy.

To overcome the limitations of presently widely used DNA array methylation arrays offering only a narrow view on the DNA methylome, we followed a different discovery and validation strategy. First, we performed whole‐genome bisulfite sequencing (WGBS) in a set of mothers alongside with their children. WGBS was carried out in 16 mother–child pairs, a rather small sample number compared to the typical sizes of epigenetic studies performed on DNA methylation arrays. However, we compensated this potential drawback by a subsequent comprehensive functional validation. We performed a detailed analysis of chromatin configuration and DNA methylation changes—including longitudinal stability analyses—and further studied genome‐wide gene expression by RNA sequencing as a functional readout of the concerted action of the observed epigenetic perturbations. In a targeted analysis, we finally validate selected findings in the entire discovery cohort.