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Chunk #5 — Results — Widespread DNAm changes contrast fetal from postnatal life

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Mapping DNA methylation across development, genotype and schizophrenia in the human frontal cortex.
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These differentially methylated CpGs were classified into differentially methylated regions (DMRs) based on a “bump hunting” approach18 requiring at least 10% changes in DNAm at adjacent CpGs, resulting in 6,480 statistically significant DMRs (at family-wide error rate, FWER < 5%, Figure 1B, Supplementary Table 2, Supplementary Figure 2, median width=74bp) which overlap (within 5kb) 4,557 unique genes, which were strongly enriched for gene sets related to brain development and morphogenesis (Supplementary Table 3, Supplementary Text 1). We additionally identified 896 regions of long-range differential methylation (Figure 1C), termed “blocks”19, using an approach adapted to the Illumina 450k20 from whole genome bisulfite sequencing (WGBS) data (median width = 91.8kb, Supplementary Table 4). These blocks overlapped a combined 731 genes that were significantly enriched for 97 GO gene sets (at pbonf < 0.05, see Supplementary Table 5), largely related again to brain development, including neuron differentiation (109/1201 genes in set, p=6.99×10−18), generation of neurons (114/1308, p=2.23×10−17), and axonogenesis (65/569 genes, p=1.73×10−15). We further found significant overlap of differentially methylated blocks with previously identified blocks associated with cancer (791 of the 896 blocks;