Genome-wide DNA methylation comparison between live human brain and peripheral tissues within individuals
Genome-wide DNA methylation comparison between live human brain and peripheral tissues within individuals
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DOI：
10.1038/s41398-019-0376-y
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发表时间：
2019-01-31
影响因子：
6.8
通讯作者：
Shinozaki, Gen
中科院分区：
文献类型：
--
作者：
Braun, Patricia R.;Han, Shizhong;Shinozaki, Gen
大脑中的差异DNA甲基化与许多精神疾病有关，但脑组织的获取基本上仅限于死后样本。替代组织的使用在鉴定与精神疾病相关的甲基化变化方面已经变得很常见。在这项研究中，我们确定了外周组织在多大程度上可以用作大脑中DNA甲基化的替代物。收集了27例接受脑切除术的难治性癫痫患者（年龄范围5-61岁）的血液、唾液、口腔和活脑组织样本。使用Infinium HumanMethylation 450（n=12）和HumanMethylationEPIC BeadChip阵列（n=21）评估全基因组甲基化。对于受试者中每个CpG平均的EPIC甲基化数据，唾液-脑相关性（r=0.90）高于血脑（r=0.86）和颊-脑（r=0.85）比较。然而，在个体CpG中，与口腔组织（17.4%）和唾液（15.1%）相比，血液具有与脑相关的名义上显著水平的最高比例的CpG（20.8%）。对于每个CpG和每个基因，脑-外周组织相关性的水平变化很大。这表明，为了确定最有用的替代组织代表脑DNA甲基化，必须考虑特定于感兴趣的基因组区域的模式。为了帮助实现这一目标，我们开发了一个网站IMAGE-CpG，允许研究人员在用户定义的基因组位置上查询DNA甲基化水平和跨组织相关程度。
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.