BACKGROUND Non-alcoholic fatty liver disease is the most common chronic liver disease in children in western countries. Adverse early-life exposures are associated with higher liver fat percentages in children. Differential DNA methylation may underlie these associations. We aimed to identify differential DNA methylation in newborns and children associated with liver fat accumulation in childhood. We also examined whether DNA methylation at 22 cytosine-phosphate-guanine sites (CpGs) associated with adult non-alcoholic fatty liver disease is associated with liver fat in children. Within a population-based prospective cohort study, we analyzed epigenome-wide DNA methylation data of 785 newborns and 344 10-year-old children in relation to liver fat fraction at 10 years. DNA methylation was measured using the Infinium HumanMethylation450 BeadChip (Illumina). We measured liver fat fraction by Magnetic Resonance Imaging. Associations of single CpG DNA methylation at the two-time points with liver fat accumulation were analyzed using robust linear regression models. We also analyzed differentially methylation regions using the dmrff package. We looked-up associations of 22 known adult CpGs at both ages with liver fat at 10 years. RESULTS The median liver fat fraction was 2.0% (95% range 1.3, 5.1). No single CpGs and no differentially methylated regions were associated with liver fat accumulation. None of the 22 known adult CpGs were associated with liver fat in children. CONCLUSIONS DNA methylation at birth and in childhood was not associated with liver fat accumulation in 10-year-old children in this study. This may be due to modest sample sizes or DNA methylation changes being a consequence rather than a determinant of liver fat.

中文翻译：

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学龄儿童的新生儿和儿童差异DNA甲基化和肝脂肪。

背景技术非酒精性脂肪肝是西方国家儿童中最常见的慢性肝病。不良的早期生命暴露与儿童较高的肝脂肪百分比有关。DNA甲基化差异可能是这些关联的基础。我们的目的是鉴定与儿童期肝脂肪蓄积有关的新生儿和儿童中的差异DNA甲基化。我们还检查了与成人非酒精性脂肪肝疾病相关的22个胞嘧啶-磷酸-鸟嘌呤位点（CpGs）的DNA甲基化是否与儿童肝脂肪相关。在一项基于人群的前瞻性队列研究中，我们分析了785个新生儿和344个10岁儿童在表观基因组范围内的DNA甲基化数据，这些数据与10年时的肝脂肪含量有关。使用Infinium HumanMethylation450 BeadChip（Illumina）测量DNA甲基化。我们通过磁共振成像测量了肝脏脂肪含量。使用稳健的线性回归模型分析了两个时间点的单CpG DNA甲基化与肝脂肪蓄积的关联。我们还使用dmrff软件包分析了差异甲基化区域。我们调查了两个年龄的22个已知成人CpG与10年肝脂肪的关联。结果中位肝脂肪分数为2.0％（95％范围1.3、5.1）。没有单一的CpGs和没有差异甲基化的区域与肝脏脂肪积累有关。儿童中22种已知的成人CpGs均与肝脂肪无关。结论在这项研究中，出生时和儿童期的DNA甲基化与10岁儿童的肝脂肪蓄积无关。