Edgar R D, Jones M J, Meaney M J, Turecki G, Kobor M S
Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
Centre for Molecular Medicine and Therapeutics, BC Children's Hospital, Vancouver, BC, Canada.
Transl Psychiatry. 2017 Aug 1;7(8):e1187. doi: 10.1038/tp.2017.171.
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.
组织差异是导致人类DNA甲基化组变异的最大因素之一。尽管DNA甲基化具有组织特异性，但由于人类大脑样本难以获取，在研究DNA甲基化与脑功能及健康之间的关联时，经常需要使用血液等替代组织。在这种情况下，人类替代组织研究的结果很难解释，因为血液与大脑DNA甲基化之间的联系很微弱且记录不充分。在此，我们旨在为学界提供一种资源，以帮助在脑组织背景下解读基于血液的DNA甲基化结果。我们使用了来自16名个体的三个脑区和全血的配对样本，在Illumina 450K人类甲基化芯片上进行检测，以量化组织间DNA甲基化的一致性。基于这些数据，我们提供了以下指标：血液和大脑样本中胞嘧啶-磷酸-鸟嘌呤二核苷酸（CpG）的变异性、血液与大脑中CpG的一致性，以及通过网络应用程序BECon（血脑表观遗传一致性；https://redgar598.shinyapps.io/BECon/）对血液和大脑中细胞组成对CpG影响强度的估计。我们预计BECon将能够在脑组织背景下对基于血液的人类DNA甲基化结果进行生物学解读。
