Abstract
Tissue differences are one of the largest contributors to variability in the human DNA methylome. Despite the tissue-specific nature of DNA methylation, the inaccessibility of human brain samples necessitates the frequent use of surrogate tissues such as blood, in studies of associations between DNA methylation and brain function and health. Results from studies of surrogate tissues in humans are difficult to interpret in this context, as the connection between blood–brain DNA methylation is tenuous and not well-documented. Here, we aimed to provide a resource to the community to aid interpretation of blood-based DNA methylation results in the context of brain tissue. We used paired samples from 16 individuals from three brain regions and whole blood, run on the Illumina 450 K Human Methylation Array to quantify the concordance of DNA methylation between tissues. From these data, we have made available metrics on: the variability of cytosine-phosphate-guanine dinucleotides (CpGs) in our blood and brain samples, the concordance of CpGs between blood and brain, and estimations of how strongly a CpG is affected by cell composition in both blood and brain through the web application BECon (Blood–Brain Epigenetic Concordance; https://redgar598.shinyapps.io/BECon/). We anticipate that BECon will enable biological interpretation of blood-based human DNA methylation results, in the context of brain.
Highlights
Research exploring the associations and underlying mechanisms of complex traits such as brain function and health have primarily focused on genetic variation, with some success.[1,2,3,4]
The model of DNA methylation (DNAm) as a mediator of complex traits has produced a surge of DNAm-based, epigenome-wide association studies (EWAS) in brain research with promising results
As we found concordance to be highly cytosine-phosphate-guanine dinucleotides (CpGs) dependent, blood-based studies do need to be carefully interpreted in the context of tissuesspecific DNAm differences
Summary
Research exploring the associations and underlying mechanisms of complex traits such as brain function and health have primarily focused on genetic variation, with some success.[1,2,3,4] Interindividual variation in brain function and health emerges as a result of both genetic variation and environmental influences. There is considerable evidence for the idea that environmentally regulated epigenetic states might form the biological basis for gene × environment interactions.[5,6,7,8,9,10,11] DNA methylation (DNAm) is a relatively stable epigenetic mark that is amenable to genomewide assessment in biosamples from human subjects in studies of complex traits. Studies of mammalian models of stress, anxiety, addiction and brain cell composition support the hypothesis that DNA methylation patterns are associated with the brain function and health.[12,13,14,15,16,17] there is evidence from human samples of specific patterns of DNAm linked to schizophrenia, autism, bipolar disorder and major psychosis.[18,19,20,21,22]
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