450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy.
450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy.
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DOI：
10.1289/ehp.1205412
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发表时间：
2012-10
影响因子：
10.4
通讯作者：
London SJ
中科院分区：
文献类型：
--
作者：
Joubert BR;Håberg SE;Nilsen RM;Wang X;Vollset SE;Murphy SK;Huang Z;Hoyo C;Midttun Ø;Cupul-Uicab LA;Ueland PM;Wu MC;Nystad W;Bell DA;Peddada SD;London SJ
背景资料：表观遗传修饰，如DNA甲基化，由于在子宫内暴露可能在儿童和成人疾病的早期编程中发挥关键作用。母亲吸烟是儿童多种不良健康结果的主要风险因素，但其潜在机制尚不清楚。目的：探讨新生儿脐血表观基因组甲基化与母亲孕期吸烟的关系。研究方法：我们使用Infinium HumanMethylation 450 BeadChip（450 K）检测了挪威母子队列研究（MoBa）中1，062份新生儿脐带血样本中妊娠期间测量的母体血浆可替宁（吸烟的客观生物标志物）与473，844个CpG位点（CpG）DNA甲基化的关系。结果：我们发现，在表观基因组范围内的统计学意义（p值< 1.06 × 10-7）的26个CpG定位到10个基因的差异DNA甲基化。我们在美国出生队列中复制了AHRR，CYP 1A 1和GFI 1中CpG的研究结果，具有严格的Bonferroni校正统计学显著性。AHRR和CYP 1A 1在芳香烃受体信号通路中起关键作用，介导烟草烟雾成分的解毒。GFI 1参与多种发育过程，但以前没有涉及对烟草烟雾的反应。结论：我们确定了一组在母亲怀孕期间吸烟的儿童出生时存在甲基化变化的基因。这是第一个使用450 K平台研究与怀孕期间母亲吸烟有关的基因组差异甲基化的研究。我们的研究结果暗示了与子宫内暴露相关的不良健康结果的发病机制中的表观遗传机制。
Background: Epigenetic modifications, such as DNA methylation, due to in utero exposures may play a critical role in early programming for childhood and adult illness. Maternal smoking is a major risk factor for multiple adverse health outcomes in children, but the underlying mechanisms are unclear. Objective: We investigated epigenome-wide methylation in cord blood of newborns in relation to maternal smoking during pregnancy. Methods: We examined maternal plasma cotinine (an objective biomarker of smoking) measured during pregnancy in relation to DNA methylation at 473,844 CpG sites (CpGs) in 1,062 newborn cord blood samples from the Norwegian Mother and Child Cohort Study (MoBa) using the Infinium HumanMethylation450 BeadChip (450K). Results: We found differential DNA methylation at epigenome-wide statistical significance (p-value < 1.06 × 10–7) for 26 CpGs mapped to 10 genes. We replicated findings for CpGs in AHRR, CYP1A1, and GFI1 at strict Bonferroni-corrected statistical significance in a U.S. birth cohort. AHRR and CYP1A1 play a key role in the aryl hydrocarbon receptor signaling pathway, which mediates the detoxification of the components of tobacco smoke. GFI1 is involved in diverse developmental processes but has not previously been implicated in responses to tobacco smoke. Conclusions: We identified a set of genes with methylation changes present at birth in children whose mothers smoked during pregnancy. This is the first study of differential methylation across the genome in relation to maternal smoking during pregnancy using the 450K platform. Our findings implicate epigenetic mechanisms in the pathogenesis of the adverse health outcomes associated with this important in utero exposure.
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影响因子：
4.4
作者：
Bibikova, Marina;Barnes, Bret;Shen, Richard
通讯作者：
Shen, Richard
DOI：
10.1007/s00428-009-0847-2
发表时间：
2010-01
期刊：
Virchows Archiv : an international journal of pathology
影响因子：
--
作者：
Feinberg AP
通讯作者：
Feinberg AP
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
DOI：
10.1073/pnas.0703739104
发表时间：
2007-08-07
影响因子：
11.1
作者：
Dolinoy, Dana C.;Huang, Dale;Jirtle, Randy L.
通讯作者：
Jirtle, Randy L.
影响因子：
7.7
作者：
Magnus, Per;Irgens, Lorentz M.;Stoltenberg, Camilla
通讯作者：
Stoltenberg, Camilla