Analysis of DNA methylation and hydroxymethylation data
Average levels of 5-mC and 5-hmC for each sample were calculated at different genomic annotations defined by chromatin immunoprecipitation sequencing (ChIP-seq), DNase-sequencing, and 15 chromatin states provided by Roadmap Epigenomics project [T tests were used to compare average hydroxymethylation change over time in the unaffected mutation carriers against the change in the controls for each annotation separately and for comparing the differences in the proportions of hypermethylated loci at peripheral blood mononuclear cells (PBMCs) enhancers. For transcription factor (TF) binding sites, we used ChIP-seq data from ENCODE [