Concordance of Human Blood and Brain DNA Methylation

Rachel Edgar, Research Assistant – Kobor Lab, UBC

DNA methylation and other epigenetic marks are emerging as an important aspect of human health and disease and as such, have an impact on multiple biomedical research disciplines. Of the latter, the field of neurobiology and behavior is among the most active and promising areas yet it has to deal with serious limitations imposed by a key feature of epigenetic biology, the tissue-specific nature of many marks. Specifically, it is impossible in the context of human population studies to directly ascertain epigenetic patterns in the brain, and thus investigations are limited to surrogate accessible tissues such as blood. Given the rapidly growing number of prominent studies reporting DNA methylation patterns in blood associated with behavioral or neurobiological phenotypes, it is both necessary and timely to carefully assess the extent to which epigenetic measures in blood report on epigenetic marks in brain.

We have analysed the concordance of DNA methylation in 16 samples of matched blood and 3 brain regions, from the Illumina 450K array. We performed Spearman correlations on the matched samples, using blood and each of our three brain regions separately. We found that matched samples showed more positive correlations than the simulated unmatched datasets, and this increased significantly when CpGs were parsed according to the extent of variation. We have successfully identified CpGs which show high concordance between blood and brain, where blood methylation may be predictive of brain methylation. We can conclude that CpGs in the human genome have varying levels of appropriateness for drawing conclusions about brain methylation from a blood surrogate.