Methylation analysis by targeted bisulfite sequencing in large for gestational age (LGA) newborns: the LARGAN cohort.
Methylation analysis by targeted bisulfite sequencing in large for gestational age (LGA) newborns: the LARGAN cohort.
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通过靶向亚硫酸氢盐测序分析大于胎龄（LGA）新生儿的甲基化：LARGAN队列。
DOI：
10.1186/s13148-023-01612-8
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发表时间：
2023-12-13
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
--
作者：
1990年，大卫巴克提出，产前营养与成人心血管疾病直接相关。从那时起，成人心血管风险，代谢综合征和出生体重之间的关系已被广泛记录。在这里，我们使用TruSeq甲基捕获EPIC平台来比较来自LARGAN队列的大于胎龄（LGA）与适于胎龄（阿加）新生儿的脐带血中的甲基化模式。在LGA和阿加组之间，我们发现了1672个差异甲基化CpG（DMC），标称p < 0.05，48个差异甲基化区域（DMR），校正p < 0.05。系统生物学方法鉴定了显著富集与FDR < 0.05的DMC相关的基因的几种生物过程，包括转录调节、肾上腺素分泌调节、去甲肾上腺素生物合成、受体反式激活、前脑区域化和与肾和心血管发育相关的几个术语。与48个DMR相关的基因的基因本体分析确定了几个显著富集的与肾脏发育相关的生物学过程，包括中肾管发育和肾单位小管发育。此外，我们的数据集确定了几个DNA甲基化标记物，这些标记物富集在涉及心血管系统、肾脏和代谢的生物学途径和罕见疾病的基因网络中。我们的研究确定了几种与胎儿过度生长相关的DMC/DMR。使用脐带血作为鉴定DNA甲基化生物标志物的材料，使我们有可能在相同的患者成长过程中对其进行随访研究。这些研究不仅将帮助我们了解甲基化组如何对连续的出生后生长做出反应，而且还将DNA甲基化组的早期改变与后来的生长和代谢适应性的临床标志物联系起来。在线版本包含补充材料，可通过10.1186/s13148-023-01612-8获得。
In 1990, David Barker proposed that prenatal nutrition is directly linked to adult cardiovascular disease. Since then, the relationship between adult cardiovascular risk, metabolic syndrome and birth weight has been widely documented. Here, we used the TruSeq Methyl Capture EPIC platform to compare the methylation patterns in cord blood from large for gestational age (LGA) vs adequate for gestational age (AGA) newborns from the LARGAN cohort. We found 1672 differentially methylated CpGs (DMCs) with a nominal p < 0.05 and 48 differentially methylated regions (DMRs) with a corrected p < 0.05 between the LGA and AGA groups. A systems biology approach identified several biological processes significantly enriched with genes in association with DMCs with FDR < 0.05, including regulation of transcription, regulation of epinephrine secretion, norepinephrine biosynthesis, receptor transactivation, forebrain regionalization and several terms related to kidney and cardiovascular development. Gene ontology analysis of the genes in association with the 48 DMRs identified several significantly enriched biological processes related to kidney development, including mesonephric duct development and nephron tubule development. Furthermore, our dataset identified several DNA methylation markers enriched in gene networks involved in biological pathways and rare diseases of the cardiovascular system, kidneys, and metabolism. Our study identified several DMCs/DMRs in association with fetal overgrowth. The use of cord blood as a material for the identification of DNA methylation biomarkers gives us the possibility to perform follow-up studies on the same patients as they grow. These studies will not only help us understand how the methylome responds to continuum postnatal growth but also link early alterations of the DNA methylome with later clinical markers of growth and metabolic fitness. The online version contains supplementary material available at 10.1186/s13148-023-01612-8.
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影响因子：
3.8
作者：
Haworth, Kim E.;Farrell, William E.;Fryer, Anthony A.
通讯作者：
Fryer, Anthony A.
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Corrada Bravo H
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Asif S;Morrow NM;Mulvihill EE;Kim KH
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Kim KH
影响因子：
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影响因子：
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作者：
Cardwell, C. R.;Stene, L. C.;Patterson, C. C.
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Patterson, C. C.