A Cell Epigenotype Specific Model for the Correction of Cellular Heterogeneity in the Brain

Cellular heterogeneity may bias cell type specific epigenetic patterns leading to a dramatic increase in false positive or negative findings in psychiatric epigenetic studies. To address this issue, we performed fluorescence activated cell sorting (FACS) of neuronal nuclei in post mortem frontal cortex 58 samples followed by Illumina HM450 microarray based DNA methylation profiling. We characterized the extent of neuron and glia specific DNA methylation variation independent of disease status and identified significant cell type specific epigenetic variation at 51% of loci. DNA methylation was profiled for sorted neuronal nuclei from post mortem frontal cortex of 29 major depression and 29 matched control samples using Illumina HM450 microarrays