Genome-wide DNA methylation comparison between live human brain and peripheral tissues within individuals

Abstract

Differential DNA methylation in the brain is associated with many psychiatric diseases, but access to brain tissues is essentially limited to postmortem 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 DNA methylation in the brain. Blood, saliva, buccal, and live brain tissue samples from 27 patients with medically intractable epilepsy undergoing brain resection were collected (age range 5–61 years). Genome-wide methylation was assessed with the Infinium HumanMethylation450 (n = 12) and HumanMethylationEPIC BeadChip arrays (n = 21). For the EPIC methylation data averaged for each CpG across subjects, the saliva–brain correlation (r = 0.90) was higher than that for blood–brain (r = 0.86) and buccal–brain (r = 0.85) comparisons. However, within individual CpGs, blood had the highest proportion of CpGs correlated to brain at nominally significant levels (20.8%), as compared to buccal tissue (17.4%) and saliva (15.1%). 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 DNA methylation, 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 DNA methylation levels and degree of cross-tissue correlation in user-defined locations across the genome.

Alteration of the brain methylation landscape following postnatal inflammatory injury in rat pups

“…Analysis of buccal swab at term equivalent age showed that very preterm with poorer neurobehavioral outcomes had altered methylation in genes relevant to neurodevelopment and neurodegenerative disease. 32 Furthermore, DNA methylation in preterm saliva at term equivalent age, which has a higher correlation to the brain methylome compared to blood or buccal swab, 33,34 identified differential methylation of 10 protein coding genes playing a role in neural cell functions and behavioral traits development. 35 As assessed through analysis of blood spot methylation, very preterm born infants displayed until 18 years old persistent methylation changes in pathways related to nervous system and hematological system development, antigen presentation, and embryonic development when compared to term born infants.…”

Antipsychotic Medications and DNA Methylation in Schizophrenia and Bipolar Disorder: A Systematic Review

“…This is further supported in studies whose primary purpose is to identify DNA REVIEW ON THE PHARMACOEPIGENETICS OF ANTIPSYCHOTICS Burghardt et al methylation correlations across various tissues within the brain. 51 Of note, peripheral blood DNA methylation has been found to have lower correlation with brain DNA methylation whereas saliva appears to have a higher correlation. Such nuances should be considered when interpreting the utility of such studies (e.g., biomarker vs mechanism).…”

DNA methylation in the APOE gene: its link with Alzheimer’s and cardiovascular health

“…Indeed, it has been reported that patients with AD and healthy controls can be distinguished based on gene-expression patterns in blood [37]. However, the APOE gene is differently expressed between brain tissue and blood [16,17] and APOE CpGs exhibit relatively modest correlations between blood-and brain methylation [33,34,35]. Thus, blood-methylation may exhibit AD- 14 associated changes that are distinct from methylation changes in the brain or they might appear later in the course of the disorder.…”

“…33], last accessed 13.10.2019), from -0.26 to 0.40 for Brodmann area 20 (BECon: https://redgar598.shinyapps.io/BECon/,[34], last accessed 13.10.2019), and from -0.21 to 0.20 for the entorhinal cortex (https://epigenetics.essex.ac.uk/bloodbrain/,[35], last accessed 13.10.2019), with most CpGs exhibiting low correlations between brain-and blood…”