Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
PLoS One. 2009 Aug 26;4(8):e6767. doi: 10.1371/journal.pone.0006767.
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.
胞嘧啶-5 在 CpG 二核苷酸中的甲基化是影响人类特征和疾病的表观遗传的一个重要机制。除了年龄和性别等因素的影响外,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)以及健康对照者(N=96),使用现成的商业化 GoldenGate 珠阵列技术,调查了特定 DNA 甲基化图谱的遗传率及其与年龄和性别的关系。尽管由于组织类型和基因座选择问题,大多数 CpG 基因座中无法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存在可复制的显著关联。我们确定了与遗传多态性相关的单核苷酸多态性与多态性附近 DNA 甲基化水平的巨大差异(顺式效应)以及与人类基因组其他部位的 DNA 甲基化水平的微小差异(反式效应)之间的关联。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,并突出了各个基因座之间的巨大差异。鉴定出 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 甲基化与疾病的关系。
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