Genome-wide DNA Methylation Comparison between Live Human Brain and Peripheral Tissues within Individuals

Differential DNA methylation (DNAm) in the brain is associated with many psychiatric diseases, but access to brain tissues is essentially limited to post-mortem samples. The use of surrogate tissues has become common in identifying methylation changes associated with psychiatric disease. In this study, we determined the extent to which peripheral tissues can be used as surrogates for DNAm in the brain. Blood, saliva, buccal, and live brain tissue samples from 27 medically intractable epilepsy patients undergoing brain resection were collected. Genome-wide methylation was assessed with the Infinium HumanMethylation450 (n=12) and HumanMethylationEPIC BeadChip arrays (n=21). For each CpG and each gene, levels of brain-peripheral tissue correlation varied widely. This indicates that to determine the most useful surrogate tissue for representing brain DNAm, the patterns specific to the genomic region of interest must be considered. To assist in that objective, we have developed a website, IMAGE-CpG, that allows researchers to interrogate DNAm levels and degree of cross-tissue correlation in user-defined locations across the genome. Genome-wide methylation was assessed with the Infinium HumanMethylation450 and HumanMethylationEPIC BeadChip arrays. The 450K dataset includes 12 subjects with brain, blood, and saliva samples. The EPIC dataset includes 21 subjects with brain, blood, buccal, and saliva samples. Additionally, fluorescence activated cell sorting (FACS) was performed to separate cells positive for a neuronal marker, resulting in five neuronal positive samples (brain_pos) and twelve neuronal negative ones (brain_neg) with sufficient DNA quantity for analysis with the EPIC array.