Maternal plasma folate impacts differential DNA methylation in an epigenome-wide meta-analysis of newborns.
Maternal plasma folate impacts differential DNA methylation in an epigenome-wide meta-analysis of newborns.
复制标题
母体血浆叶酸会影响新生儿的表观基因组元分析中的差异DNA甲基化。
DOI：
10.1038/ncomms10577
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发表时间：
2016-02-10
影响因子：
16.6
通讯作者：
London SJ
中科院分区：
文献类型：
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作者：
Joubert BR;den Dekker HT;Felix JF;Bohlin J;Ligthart S;Beckett E;Tiemeier H;van Meurs JB;Uitterlinden AG;Hofman A;Håberg SE;Reese SE;Peters MJ;Andreassen BK;Steegers EA;Nilsen RM;Vollset SE;Midttun Ø;Ueland PM;Franco OH;Dehghan A;de Jongste JC;Wu MC;Wang T;Peddada SD;Jaddoe VW;Nystad W;Duijts L;London SJ
叶酸对于胎儿发育至关重要。建议围孕期补充叶酸和食品强化以预防神经管缺陷。围孕期叶酸影响正常发育和疾病的机制尚不清楚：可能涉及表观遗传学。我们使用 Illumina 的 HumanMmethyl450 Beadchip 对来自两个欧洲队列的 1,988 名新生儿检查了怀孕期间母体血浆叶酸与表观基因组范围内的 DNA 甲基化之间的关联。在这里，我们使用荟萃分析报告综合协变量调整结果，并采用途径和基因表达分析。 443 个 CpG（320 个基因）与妊娠期间母体血浆叶酸水平显着相关（错误发现率 5%）； 48 经过 Bonferroni 校正后显着。大多数基因在叶酸生物学方面尚不为人所知，包括 APC2、GRM8、SLC16A12、OPCML、PRPH、LHX1、KLK4 和 PRSS21。有些与神经管缺陷、神经功能或胚胎发育的各个方面以外的出生缺陷有关。这些发现可能有助于了解母体叶酸如何影响后代的表观基因组发育和健康结果。 通常建议尝试怀孕的女性服用叶酸，以确保胎儿正常发育。在这里，作者进行了一项大型表观基因组学研究，以检查哪些胎儿表观遗传变化与不同的母体血浆叶酸水平相关。
Folate is vital for fetal development. Periconceptional folic acid supplementation and food fortification are recommended to prevent neural tube defects. Mechanisms whereby periconceptional folate influences normal development and disease are poorly understood: epigenetics may be involved. We examine the association between maternal plasma folate during pregnancy and epigenome-wide DNA methylation using Illumina's HumanMethyl450 Beadchip in 1,988 newborns from two European cohorts. Here we report the combined covariate-adjusted results using meta-analysis and employ pathway and gene expression analyses. Four-hundred forty-three CpGs (320 genes) are significantly associated with maternal plasma folate levels during pregnancy (false discovery rate 5%); 48 are significant after Bonferroni correction. Most genes are not known for folate biology, including APC2, GRM8, SLC16A12, OPCML, PRPH, LHX1, KLK4 and PRSS21. Some relate to birth defects other than neural tube defects, neurological functions or varied aspects of embryonic development. These findings may inform how maternal folate impacts the developing epigenome and health outcomes in offspring. Folic acid is routinely recommended for women trying to conceive to ensure proper fetal development. Here, the authors perform a large epigenomics study to examine which fetal epigenetic changes are associated with varied maternal plasma folate levels.