Effect of maternal preconceptional and pregnancy micronutrient interventions on children's DNA methylation: Findings from the EMPHASIS study.
Effect of maternal preconceptional and pregnancy micronutrient interventions on children's DNA methylation: Findings from the EMPHASIS study.
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DOI：
10.1093/ajcn/nqaa193
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发表时间：
2020-10-01
期刊：
影响因子：
--
通讯作者：
EMPHASIS Study Group
中科院分区：
文献类型：
--
作者：
Saffari A;Shrestha S;Issarapu P;Sajjadi S;Betts M;Sahariah SA;Tomar AS;James P;Dedaniya A;Yadav DK;Kumaran K;Prentice AM;Lillycrop KA;Fall CHD;Chandak GR;Silver MJ;EMPHASIS Study Group
母亲在怀孕期间的营养与后代在早期和后期的健康有关，DNA甲基化（DNAm）的变化被认为是一种介导机制。我们调查了母亲在怀孕前和怀孕期间参加2项微量营养素补充随机对照试验的儿童的干预相关DNA m变化，作为EMPHASIS（印度和撒哈拉以南非洲评估的孕前营养和健康的表观遗传机制）研究（ISRCTN 14266771）的一部分。我们使用Illumina EPIC阵列对来自印度（n = 698）和冈比亚（n = 293）儿童的血液样本进行了表观基因组关联研究，并对阵列上未选择的基因座进行了靶向研究。印度的微营养素干预措施是以食物为基础的，而冈比亚的干预措施是微营养素片剂。我们在冈比亚人中鉴定了6个差异甲基化的CpG [干预组减少2.5-5.0%，所有错误发现率（FDR）<5%]，大多数映射到ESM 1，这也代表了区域分析中的强信号。在印度队列中，一个CpG通过FDR <5%，但总体效应量很小（<1%），并且不具有稳健签名的特征。我们还发现了强有力的证据，亚稳态表观等位基因的亚阈值信号中的冈比亚分析富集。这支持了多个甲基化位点受早期胚胎中微量营养素补充影响的观点。母亲怀孕前和孕期补充微量营养素可能会改变7-9岁儿童的DNAm。多种因素，包括干预性质、参与者和环境之间的差异，可能导致印度队列中缺乏复制。与表型结局的潜在联系将在EMPHASIS研究的下一阶段进行探索。
Maternal nutrition in pregnancy has been linked to offspring health in early and later life, with changes to DNA methylation (DNAm) proposed as a mediating mechanism. We investigated intervention-associated DNAm changes in children whose mothers participated in 2 randomized controlled trials of micronutrient supplementation before and during pregnancy, as part of the EMPHASIS (Epigenetic Mechanisms linking Preconceptional nutrition and Health Assessed in India and sub-Saharan Africa) study (ISRCTN14266771). We conducted epigenome-wide association studies with blood samples from Indian (n = 698) and Gambian (n = 293) children using the Illumina EPIC array and a targeted study of selected loci not on the array. The Indian micronutrient intervention was food based, whereas the Gambian intervention was a micronutrient tablet. We identified 6 differentially methylated CpGs in Gambians [2.5–5.0% reduction in intervention group, all false discovery rate (FDR) <5%], the majority mapping to ESM1, which also represented a strong signal in regional analysis. One CpG passed FDR <5% in the Indian cohort, but overall effect sizes were small (<1%) and did not have the characteristics of a robust signature. We also found strong evidence for enrichment of metastable epialleles among subthreshold signals in the Gambian analysis. This supports the notion that multiple methylation loci are influenced by micronutrient supplementation in the early embryo. Maternal preconceptional and pregnancy micronutrient supplementation may alter DNAm in children measured at 7–9 y. Multiple factors, including differences between the nature of the intervention, participants, and settings, are likely to have contributed to the lack of replication in the Indian cohort. Potential links to phenotypic outcomes will be explored in the next stage of the EMPHASIS study.
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