Interindividual methylomic variation across blood, cortex, and cerebellum: implications for epigenetic studies of neurological and neuropsychiatric phenotypes.
Interindividual methylomic variation across blood, cortex, and cerebellum: implications for epigenetic studies of neurological and neuropsychiatric phenotypes.
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DOI：
10.1080/15592294.2015.1100786
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Mill J
中科院分区：
文献类型：
--
作者：
Hannon E;Lunnon K;Schalkwyk L;Mill J
鉴于表观遗传过程的组织特异性，疾病相关组织的评估是表观基因组关联研究（EWAS）的重要考虑因素。人们对全血等容易获取的组织是否可以用于解决大脑等难以获取的组织中的个体间表观基因组变异问题知之甚少。我们定量了从122个个体的全血和4个脑区（前额叶皮层、内嗅皮层、上级颞回和小脑）分离的匹配DNA样本中的DNA甲基化。我们探讨了组织之间的共变异以及血液中甲基化变异在多大程度上预测了大脑中鉴定的个体间变异。对于大多数DNA甲基化位点，全血中的个体间变异并不是大脑中个体间变异的强有力预测因子，尽管与皮质区域的关系比与小脑的关系更强。探针子集的变异在组织间具有很强的相关性，即使在DNA甲基化的实际水平在它们之间显著不同的情况下。然而，这种共变的很大一部分可能是由遗传影响造成的。我们的数据表明，对于大多数基因组，基于血液的EWAS用于脑被假定为主要感兴趣组织的疾病将提供与潜在病理过程相关的有限信息。然而，这些结果并没有低估使用基于血液的EWAS来鉴定大脑中表现的疾病表型的生物标志物的效用。我们已经生成了一个可检索的数据库，用于解释来自基于血液的EWAS分析的数据（http：//epigenetics.essex.ac.uk/bloodbrain/）。
Given the tissue-specific nature of epigenetic processes, the assessment of disease-relevant tissue is an important consideration for epigenome-wide association studies (EWAS). Little is known about whether easily accessible tissues, such as whole blood, can be used to address questions about interindividual epigenomic variation in inaccessible tissues, such as the brain. We quantified DNA methylation in matched DNA samples isolated from whole blood and 4 brain regions (prefrontal cortex, entorhinal cortex, superior temporal gyrus, and cerebellum) from 122 individuals. We explored co-variation between tissues and the extent to which methylomic variation in blood is predictive of interindividual variation identified in the brain. For the majority of DNA methylation sites, interindividual variation in whole blood is not a strong predictor of interindividual variation in the brain, although the relationship with cortical regions is stronger than with the cerebellum. Variation at a subset of probes is strongly correlated across tissues, even in instances when the actual level of DNA methylation is significantly different between them. A substantial proportion of this co-variation, however, is likely to result from genetic influences. Our data suggest that for the majority of the genome, a blood-based EWAS for disorders where brain is presumed to be the primary tissue of interest will give limited information relating to underlying pathological processes. These results do not, however, discount the utility of using a blood-based EWAS to identify biomarkers of disease phenotypes manifest in the brain. We have generated a searchable database for the interpretation of data from blood-based EWAS analyses (http://epigenetics.essex.ac.uk/bloodbrain/).