Epigenome-Wide Association Study Identifies Cardiac Gene Patterning and a Novel Class of Biomarkers for Heart Failure
Epigenome-Wide Association Study Identifies Cardiac Gene Patterning and a Novel Class of Biomarkers for Heart Failure
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DOI：
10.1161/circulationaha.117.027355
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发表时间：
2017-10-17
期刊：
影响因子：
37.8
通讯作者：
Posch, Andreas E.
中科院分区：
文献类型：
--
作者：
Meder, Benjamin;Haas, Jan;Posch, Andreas E.
背景：生化 DNA 修饰类似于遗传信息、环境因素和转录组之间的关键调节层。为了确定与心肌功能障碍和心力衰竭相关的表观遗传易感区域和新型生物标志物，我们对扩张型心肌病患者和对照患者的心肌组织和血液进行了首次多组学研究。 方法：使用 Infinium 人类甲基化 450 对活体先证者的左心室活检和全外周血中的 DNA 甲基化进行高密度表观基因组图谱。对相同样本并行进行 RNA 深度测序。对所有患者进行全基因组测序，排除混杂基因型诱导的甲基化调用。 结果：在筛选阶段，我们检测到 59 个与扩张型心肌病显着相关的表观遗传位点（错误发现纠正了 P
BACKGROUND: Biochemical DNA modification resembles a crucial regulatory layer among genetic information, environmental factors, and the transcriptome. To identify epigenetic susceptibility regions and novel biomarkers linked to myocardial dysfunction and heart failure, we performed the first multi-omics study in myocardial tissue and blood of patients with dilated cardiomyopathy and controls.METHODS: Infinium human methylation 450 was used for high-density epigenome-wide mapping of DNA methylation in left-ventricular biopsies and whole peripheral blood of living probands. RNA deep sequencing was performed on the same samples in parallel. Whole-genome sequencing of all patients allowed exclusion of promiscuous genotype-induced methylation calls.RESULTS: In the screening stage, we detected 59 epigenetic loci that are significantly associated with dilated cardiomyopathy (false discovery corrected P