Replicated umbilical cord blood DNA methylation loci associated with gestational age at birth.
Replicated umbilical cord blood DNA methylation loci associated with gestational age at birth.
复制标题
复制的脐带血 DNA 甲基化位点与出生胎龄相关。
DOI：
10.1080/15592294.2020.1767277
复制
发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Strauss,JeromeF
中科院分区：
文献类型：
--
作者：
York,TimothyP;Latendresse,ShawnJ;Jackson-Cook,Colleen;Lapato,DanaM;Moyer,Sara;Wolen,AaronR;Roberson-Nay,Roxann;Do,ElizabethK;Murphy,SusanK;Hoyo,Catherine;Fuemmeler,BernardF;Strauss,JeromeF
DNA甲基化对子宫内扰动高度敏感，并在胚胎发育和基因表达调控中发挥作用。胎儿遗传成分以前已被证明对出生时间有显着影响，但对单个基因的身份和行为知之甚少。本研究的目的是测试脐带血中全基因组DNA甲基化水平与出生时胎龄（GA）的相关程度。研究结果在一个独立的样本中得到验证，并在具有多组学数据的标本中评估了基因表达调控的证据。在妊娠、种族、环境、基因（PREG）和新生儿表观遗传学研究（NEST）队列中，通过Illumina Infinium Human Methylation 450 K BeadChip测量的全基因组DNA甲基化与2，372个CpG探针（5% FDR）的GA相关。有意义的探针映射到1,640个特征基因，并与附近的基因表达的测量获得的Affyellow HG-133 A微阵列的11个基因被发现。差异甲基化的位置富集了活跃转录和增强子染色质状态，主要位于CpG岛之外，并映射到炎症和先天免疫本体富集的基因。在这两个PREG和NEST，来自这些探针的第一个主成分解释约一半（58.1%和47.8%，分别）的GA的变化。所确定的基因通路与病原体检测和免疫系统反应的假设一致，以引起早产作为非计划性炎症的结果。
DNA methylation is highly sensitive toin uteroperturbations and has an established role in both embryonic development and regulation of gene expression. The foetal genetic component has been previously shown to contribute significantly to the timing of birth, yet little is known about the identity and behaviour of individual genes. The aim of this study was to test the extent genome-wide DNA methylation levels in umbilical cord blood were associated with gestational age at birth (GA). Findings were validated in an independent sample and evidence for the regulation of gene expression was evaluated forcisgene relationships in specimens with multi-omic data. Genome-wide DNA methylation, measured by the Illumina Infinium Human Methylation 450 K BeadChip, was associated with GA for 2,372 CpG probes (5% FDR) in both the Pregnancy, Race, Environment, Genes (PREG) and Newborn Epigenetic Study (NEST) cohorts. Significant probes mapped to 1,640 characterized genes and an association with nearby gene expression measures obtained by the Affymetrix HG-133A microarray was found for 11 genes. Differentially methylated positions were enriched for actively transcribed and enhancer chromatin states, were predominately located outside of CpG islands, and mapped to genes enriched for inflammation and innate immunity ontologies. In both PREG and NEST, the first principal component derived from these probes explained approximately one-half (58.1% and 47.8%, respectively) of the variation in GA. Gene pathways identified are consistent with the hypothesis of pathogen detection and response by the immune system to elicit premature labour as a consequence of unscheduled inflammation.