对儿童食欲性状的病因了解甚少。生命早期表观遗传过程可能参与儿童食欲调节的发育编程。一个这样的过程是DNA甲基化(DNAm),在DNA的特定部分添加甲基,胞嘧啶碱基在鸟嘌呤碱基旁边,CpG位点。我们荟萃分析了脐带血DNAm和幼儿食欲性状的表观全基因组关联研究(EWASs)。数据来自两个独立的队列:R代研究(n=1,086,鹿特丹,荷兰)和健康开始研究(n=236,科罗拉多州,美国)。使用IlluminaInfiniumHumanomethylation450BeadChip测量脐带血中常染色体甲基化位点的DNAm。父母报告了他们孩子的食物反应,情绪不足,使用4-5岁儿童饮食行为问卷的饱腹感反应性和食物烦躁性。使用多元回归模型来检查个体站点和区域水平(使用DMRff)的DNAm(预测因子)与每个食欲性状(结果)的关联。调整协变量。应用Bonferroni校正来调整多次测试。当检查个体CpG位点时,没有DNAm和任何食欲性状的关联。然而,当在所谓的差异甲基化区域联合检查多个CpG时,我们确定了45个DNAm与食物反应性的关联,DNAm与情绪不足的7个关联,DNAm与饱腹感反应性的13个关联,以及DNAm与食物烦躁的9个关联。这项研究表明,新生儿中的DNAm可能部分解释了儿童早期表达的食欲性状的变化,并为通过DNAm对儿童食欲性状的早期编程提供了初步支持。研究与食欲性状相关的差异DNAm可能是确定这些行为发展的生物学途径的重要第一步。
The etiology of childhood appetitive traits is poorly understood. Early-life epigenetic processes may be involved in the developmental programming of appetite regulation in childhood. One such process is DNA methylation (DNAm), whereby a methyl group is added to a specific part of DNA, where a cytosine base is next to a guanine base, a CpG site. We meta-analyzed epigenome-wide association studies (EWASs) of cord blood DNAm and early-childhood appetitive traits. Data were from two independent cohorts: the Generation R
Study (n = 1,086, Rotterdam, the Netherlands) and the Healthy Start
study (n = 236, Colorado, USA). DNAm at autosomal methylation sites in cord blood was measured using the Illumina Infinium HumanMethylation450 BeadChip. Parents reported on their child\'s food responsiveness, emotional undereating, satiety responsiveness and food fussiness using the Children\'s Eating Behaviour Questionnaire at age 4-5 years. Multiple regression models were used to examine the association of DNAm (predictor) at the individual site- and regional-level (using DMRff) with each appetitive trait (outcome), adjusting for covariates. Bonferroni-correction was applied to adjust for multiple testing. There were no associations of DNAm and any appetitive trait when examining individual CpG-sites. However, when examining multiple CpGs jointly in so-called differentially methylated regions, we identified 45 associations of DNAm with food responsiveness, 7 associations of DNAm with emotional undereating, 13 associations of DNAm with satiety responsiveness, and 9 associations of DNAm with food fussiness. This
study shows that DNAm in the newborn may partially explain variation in appetitive traits expressed in early childhood and provides preliminary support for early programming of child appetitive traits through DNAm. Investigating differential DNAm associated with appetitive traits could be an important first step in identifying biological pathways underlying the development of these behaviors.