Testing two models describing how methylome-wide studies in blood are informative for psychiatric conditions.
Testing two models describing how methylome-wide studies in blood are informative for psychiatric conditions.
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DOI：
10.2217/epi.13.36
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发表时间：
2013-08
期刊：
影响因子：
3.8
通讯作者：
van den Oord EJ
中科院分区：
文献类型：
--
作者：
Aberg KA;Xie LY;McClay JL;Nerella S;Vunck S;Snider S;Beardsley PM;van den Oord EJ
由于精神疾病的主要相关组织（大脑）通常无法获得，我们旨在基于两个模型研究血液是否可以用作甲基化研究的替代品。在“特征”模型中，甲基化与疾病之间存在关联，因为致病因素影响了血液中的甲基化。在“镜像位点”模型中，血液中的甲基化状态与大脑中相应的致病位点相关。对四只氟哌啶醇治疗和十只未治疗的 C57BL/6 小鼠的血液、皮质和海马进行甲基结合域富集和新一代测序，揭示了跨组织甲基化的高度相关性。尽管治疗诱导大量甲基化变化，但这种相关性仍然很高。我们的结果表明，与特征模型一致，影响大脑过程的因素（即氟哌啶醇）在血液中留下生物标志物特征，并且与镜像位点模型一致，血液中许多位点的甲基化状态反映了大脑中的甲基化状态。
As the primary relevant tissue (brain) for psychiatric disorders is commonly not available, we aimed to investigate whether blood can be used as a proxy in methylation studies on the basis of two models. In the ‘signature’ model methylation–disease associations occur because a disease-causing factor affected methylation in the blood. In the ‘mirror-site’ model the methylation status in the blood is correlated with the corresponding disease-causing site in the brain. Methyl-binding domain enrichment and next-generation sequencing of the blood, cortex and hippocampus from four haloperidol-treated and ten untreated C57BL/6 mice revealed high levels of correlation in methylation across tissues. Despite the treatment inducing a large number of methylation changes, this correlation remains high. Our results show that, consistent with the signature model, factors that affect brain processes (i.e., haloperidol) leave biomarker signatures in the blood and, consistent with the mirror-site model, the methylation status of many sites in the blood mirror those in the brain.