Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, Robison Hall, Memphis, TN 38152, USA.
Department of Mathematical Science, University of Memphis, Dunn Hall, Memphis, TN 38152, USA.
Nutrients. 2020 Dec 30;13(1):99. doi: 10.3390/nu13010099.
Epigenetic factors have been suggested as mediators of early-life nutrition to future health. Prior studies focused on breastfeeding effects on DNA methylation (DNAm), ignoring other feeding modes. In this analysis of the Isle of Wight birth cohort, feeding modes were categorized as exclusive breastfeeding (EBF), exclusive formula feeding (EFF), and mixed feeding based on whether the respective feeding mode lasted for at least 3 months. In addition, in the past, infant feeding modes were assessed using DNAm at one time point in childhood, not changes of DNAm. In this paper, methylation differences (delta DNAm) were calculated by subtracting residual methylation values at birth from age 10 years (adjusting for cell types and season of blood collection at both ages). These deltas were estimated for all methylation sites where cytosine was followed by guanine (cytosine guanine dinucleotide (CpG) sites). Then, we performed an epigenome-wide association study contrasting EBF, EFF, and mixed feeding with delta DNAm that represents changes in methylation from birth to 10 years. A total of 87 CpGs (EBF: 27 CpGs, EFF: 48 CpGs, mixed: 12 CpGs) were identified using separate linear regression models adjusting for confounders and multiple testing. The sum of all changes in methylation from birth to age 10 years was significantly lower in the EFF group. Correspondingly, the number of CpGs with a methylation decline was 4.7% higher reflecting 13,683 CpGs. Lower methylation related to exclusive formula feeding and its adverse potential for the child's development needs future research to reduce adverse health effects.
表观遗传因素被认为是早期营养对未来健康的中介。先前的研究集中在母乳喂养对 DNA 甲基化（DNAm）的影响，而忽略了其他喂养方式。在对怀特岛出生队列的这项分析中，喂养方式被分为纯母乳喂养（EBF）、纯配方奶喂养（EFF）和混合喂养，这取决于各自的喂养方式是否至少持续 3 个月。此外，过去，婴儿喂养方式是通过在儿童时期的一个时间点评估 DNAm，而不是评估 DNAm 的变化。在本文中，通过从出生时减去 10 岁时的残留甲基化值来计算甲基化差异（delta DNAm）（调整两个年龄时的细胞类型和采血季节）。这些差值是针对所有紧随其后的胞嘧啶的甲基化位点（胞嘧啶鸟嘌呤二核苷酸（CpG）位点）计算的。然后，我们进行了全基因组关联研究，将 EBF、EFF 和混合喂养与代表从出生到 10 岁甲基化变化的 delta DNAm 进行对比。使用单独的线性回归模型，在调整混杂因素和多重检验后，总共鉴定出 87 个 CpG（EBF：27 个 CpG，EFF：48 个 CpG，混合：12 个 CpG）。EFF 组从出生到 10 岁的所有甲基化变化总和明显较低。相应地，甲基化下降的 CpG 数量增加了 4.7%，反映了 13683 个 CpG。与纯配方奶喂养相关的较低甲基化及其对儿童发育的潜在不利影响需要进一步研究，以减少不良健康影响。
