We identified changes in DNA methylation associated with genetic sequence and developmental stage in one of the largest studies of postmortem human brain tissue to date. The most extensive changes in the epigenome are found at local, regional, and long-range spatial resolutions in comparing prenatal and postnatal specimens that we suggest likely represent in part shifts in neuronal composition across the lifespan, and correspond to strong changes in gene expression profiles. Interestingly, these developmentally associated changes in DNAm were significantly enriched for genomic regions that confer clinical risk for schizophrenia. Many risk variants across the catalog of GWAS positive loci in studies of common medical disorders themselves associate with nearby DNAm levels, termed meQTLs, suggesting potential mechanisms by which genetic risk propagates in the population. Lastly, we show that several thousand individual CpGs demonstrate small but statistically significant difference in DNAm levels comparing adult patients with schizophrenia with controls that did not appear confounded by cellular composition or smoking. The differences found between patients and controls appear to represent epigenetic marks that principally associate with early neurodevelopment and not with
