Novel regional age-associated DNA methylation changes within human common disease-associated loci.
Novel regional age-associated DNA methylation changes within human common disease-associated loci.
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DOI：
10.1186/s13059-016-1051-8
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发表时间：
2016-09-23
期刊：
影响因子：
12.3
通讯作者：
Spector TD
中科院分区：
文献类型：
--
作者：
Bell CG;Xia Y;Yuan W;Gao F;Ward K;Roos L;Mangino M;Hysi PG;Bell J;Wang J;Spector TD
随着年龄的增长，慢性病的风险和严重程度逐渐受到影响。它还修饰表观基因组，由于随机漂移和特定功能基因座内的变异，DNA甲基化发生变化。在一组2238个年龄在19-82岁的外周血全基因组DNA甲基化组的发现中，我们从NIH全基因组关联研究目录中的单核苷酸多态性的连锁不平衡块中确定了71个与年龄相关的差异甲基化区域。这包括52个新区域，其中29个位于450 k或27 k Illumina阵列未覆盖的基因座内，并且在整个组织范围内富集了DNase-I超敏位点。这些与年龄相关的差异甲基化区域也显示出在多种细胞类型中增强子和平衡启动子的显著富集。在2084个DNA甲基化组的复制集中，95.7%的年龄相关差异甲基化区域显示出相同的衰老效应方向，其中80.3%和53.5%的复制分别达到p < 0.05和p < 1.85 × 10-8。通过分析人类基因组中功能丰富的疾病和性状相关区域，我们确定了新的表观遗传衰老变化，这些变化可能是有用的生物标志物，或为与年龄相关的常见疾病提供机制性见解。本文的在线版本（doi：10.1186/s13059-016-1051-8）包含补充材料，可供授权用户使用。
Advancing age progressively impacts on risk and severity of chronic disease. It also modifies the epigenome, with changes in DNA methylation, due to both random drift and variation within specific functional loci. In a discovery set of 2238 peripheral-blood genome-wide DNA methylomes aged 19–82 years, we identify 71 age-associated differentially methylated regions within the linkage disequilibrium blocks of the single nucleotide polymorphisms from the NIH genome-wide association study catalogue. This included 52 novel regions, 29 within loci not covered by 450 k or 27 k Illumina array, and with enrichment for DNase-I Hypersensitivity sites across the full range of tissues. These age-associated differentially methylated regions also show marked enrichment for enhancers and poised promoters across multiple cell types. In a replication set of 2084 DNA methylomes, 95.7 % of the age-associated differentially methylated regions showed the same direction of ageing effect, with 80.3 % and 53.5 % replicated to p < 0.05 and p < 1.85 × 10–8, respectively. By analysing the functionally enriched disease and trait-associated regions of the human genome, we identify novel epigenetic ageing changes, which could be useful biomarkers or provide mechanistic insights into age-related common diseases. The online version of this article (doi:10.1186/s13059-016-1051-8) contains supplementary material, which is available to authorized users.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
30.8
作者：
通讯作者：
--
DOI：
10.1073/pnas.0500398102
发表时间：
2005-07-26
影响因子：
11.1
作者：
Fraga, MF;Ballestar, E;Esteller, M
通讯作者：
Esteller, M
影响因子：
12.3
作者：
Halachev K;Bast H;Albrecht F;Lengauer T;Bock C
通讯作者：
Bock C