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Comparative Study
. 2019 Jan 31;9(1):47.
doi: 10.1038/s41398-019-0376-y.

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

Patricia R Braun  1   2   3 , Shizhong Han  1   2   3 , Benjamin Hing  1 , Yasunori Nagahama  4 , Lindsey N Gaul  1 , Jonathan T Heinzman  1 , Andrew J Grossbach  4   5 , Liesl Close  4 , Brian J Dlouhy  4 , Matthew A Howard 3rd  4 , Hiroto Kawasaki  4 , James B Potash  1   2   3 , Gen Shinozaki  6   7   8
Affiliations
Comparative Study

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

Patricia R Braun et al. Transl Psychiatry. .

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.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Multidimensional scaling (MDS) plot of genome-wide DNAm levels from brain, saliva, blood, buccal samples (n = 21) and FAC-sorted brain samples (neu(+) n = 5, neu(−) n = 12) analyzed on the Illumina EPIC array
Fig. 2
Fig. 2
Histograms of the distribution of correlations (r) of the individual 822,996 CpGs covered on the EPIC array between the brain and a blood, b buccal, and c saliva tissues (n = 21)
Fig. 3
Fig. 3
Degree of DNAm correlation of all CpG probes between each peripheral tissue and brain for all subjects
Fig. 4
Fig. 4
DNAm correlation comparisons of CpGs located in different genomic and functional contexts taken from the average DNAm for each tissue
See this image and copyright information in PMC

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