The relationship of DNA methylation with age, gender and genotype in twins and healthy controls.
The relationship of DNA methylation with age, gender and genotype in twins and healthy controls.
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DOI：
10.1371/journal.pone.0006767
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发表时间：
2009-08-26
期刊：
影响因子：
3.7
通讯作者：
Ophoff RA
中科院分区：
文献类型：
--
作者：
Boks MP;Derks EM;Weisenberger DJ;Strengman E;Janson E;Sommer IE;Kahn RS;Ophoff RA
CpG二核苷酸中的胞嘧啶-5甲基化是表观遗传学影响人类特征和疾病的潜在重要机制。除了年龄和性别的影响外，最近还描述了DNA甲基化水平的遗传控制。我们使用了一组双胞胎中的全血基因组DNA(23对MZ双胞胎和23对DZ双胞胎，N = 92)以及健康对照组(N = 96)，利用现成的商业金门微珠阵列技术，研究了选定的DNA甲基化图谱的遗传性及其与年龄和性别的关系。尽管由于组织类型和位点选择问题，无法在大多数CpG基因座上检测到有意义的甲基化差异，但我们发现DNA甲基化与年龄和性别之间存在可复制的显著关联。我们确定了遗传上可遗传的单核苷酸多态与多态附近DNA甲基化水平的大差异(顺式效应)以及与人类基因组其他地方DNA甲基化水平的小得多的差异(反式效应)的关联。我们的结果证明了基于阵列的方法在DNA甲基化研究中的可行性，并突出了单个基因座之间的巨大差异。识别DNA甲基化水平受遗传控制或与年龄或性别相关的CpG基因座，将有助于进一步研究DNA甲基化与疾病的作用。
Cytosine-5 methylation within CpG dinucleotides is a potentially important mechanism of epigenetic influence on human traits and disease. In addition to influences of age and gender, genetic control of DNA methylation levels has recently been described. We used whole blood genomic DNA in a twin set (23 MZ twin-pairs and 23 DZ twin-pairs, N = 92) as well as healthy controls (N = 96) to investigate heritability and relationship with age and gender of selected DNA methylation profiles using readily commercially available GoldenGate bead array technology. Despite the inability to detect meaningful methylation differences in the majority of CpG loci due to tissue type and locus selection issues, we found replicable significant associations of DNA methylation with age and gender. We identified associations of genetically heritable single nucleotide polymorphisms with large differences in DNA methylation levels near the polymorphism (cis effects) as well as associations with much smaller differences in DNA methylation levels elsewhere in the human genome (trans effects). Our results demonstrate the feasibility of array-based approaches in studies of DNA methylation and highlight the vast differences between individual loci. The identification of CpG loci of which DNA methylation levels are under genetic control or are related to age or gender will facilitate further studies into the role of DNA methylation and disease.
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影响因子：
3.7
作者：
Alberts, Rudi;Terpstra, Peter;Li, Yang;Breitling, Rainer;Nap, Jan-Peter;Jansen, Ritsert C.
通讯作者：
Jansen, Ritsert C.
影响因子：
3.5
作者：
Heijmans, Bastiaan T.;Kremer, Dennis;Slagboom, P. Eline
通讯作者：
Slagboom, P. Eline
影响因子：
64.5
作者：
Goldberg, Aaron D.;Allis, C. David;Bernstein, Emily
通讯作者：
Bernstein, Emily
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：
--
作者：
Chu, Michelle W.;Siegmund, Kimberly D.;Shibata, Darryl
通讯作者：
Shibata, Darryl