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Chunk #3 — 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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We obtained high quality DNAm data on 526 subjects from across the lifespan, including adults diagnosed with schizophrenia (Supplementary Table 1) using the Illumina 450k microarray (see Methods) after removing probes on the sex chromosomes and those containing known SNPs at the single base extension and target CpG sites, leaving 456,513 autosomal probes for analysis. We compared fetal (n=35) and post-natal (n=300) non-psychiatric control samples (including newborns and children) to identify changes in DNAm associated with the transition from the second fetal trimester to postnatal life, at varying spatial scales, adjusting for negative control probe factors to control for potential “batch” effects (see Methods). At the single probe level, the majority of assayed CpGs (N=231,415, 50.7%) were significantly differentially methylated (at Bonferroni-adjusted p-value, pbonf < 0.05, corresponding to p < 1.10×10−7, Online Table 1), suggesting a vastly different epigenetic landscape of the prefrontal cortex, during fetal compared with postnatal life (Figure 1A). While the Illumina 450k largely targets CpGs in and around gene promoter regions (islands, shores and shelves)17, almost every annotated gene (17,300/19,771 via UCSC knownGene hg19 table, 87.5%)