DNA Methylation Patterns in Cord Blood of Neonates Across Gestational Age: Association With Cell-Type Proportions.
DNA Methylation Patterns in Cord Blood of Neonates Across Gestational Age: Association With Cell-Type Proportions.
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DOI：
10.1097/nnr.0000000000000210
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发表时间：
2017
期刊：
影响因子：
2.5
通讯作者：
Corrada Bravo H
中科院分区：
文献类型：
--
作者：
Braid SM;Okrah K;Shetty A;Corrada Bravo H
统计方法可用于估计表观全基因组关联研究（EWAS）中使用的成人全血标本中细胞类型（细胞异质性）的比例。然而，没有方法来估计EWAS中使用的脐带血（也是异质组织）中细胞类型的比例。本研究的目的是确定脐带血中DNA甲基化（DNAm）模式的差异是否是通常发生在胎龄期间的血细胞类型比例变化的结果，并通过比较暴露于和未暴露于产前类固醇的早产儿来证明细胞类型比例混杂的影响。我们使用Illumina HumanMethylation27k BeadChip阵列获得了来自波士顿出生队列的385名新生儿的脐带血DNA图谱。我们估计六种细胞类型的细胞类型的比例使用的去卷积方法开发的。细胞类型比例估计值分为两组，这两组在胎龄上存在显著差异，表明胎龄与细胞类型比例相关。在产前暴露于类固醇的婴儿中，在控制细胞类型比例后，差异甲基化CpG的数量从127下降到1。使用脐带血的EWAS受到细胞类型比例的混淆。仔细的研究设计，包括校正细胞类型比例和解释使用脐带血的EWAS结果是至关重要的。
A statistical methodology is available to estimate the proportion of cell types (cellular heterogeneity) in adult whole blood specimens used in epigenome-wide association studies (EWAS). However, there is no methodology to estimate the proportion of cell types in umbilical cord blood (also a heterogeneous tissue) used in EWAS. The objectives of this study were to determine whether differences in DNA methylation (DNAm) patterns in umbilical cord blood are the result of blood cell type proportion changes that typically occur across gestational age and to demonstrate the effect of cell type proportion confounding by comparing preterm infants exposed and not exposed to antenatal steroids. We obtained DNAm profiles of cord blood using the Illumina HumanMethylation27k BeadChip array for 385 neonates from the Boston Birth Cohort. We estimated cell type proportions for six cell types using the deconvolution method developed by. The cell type proportion estimates segregated into two groups that were significantly different by gestational age, indicating that gestational age was associated with cell type proportion. Among infants exposed to antenatal steroids, the number of differentially methylated CpGs dropped from 127 to 1 after controlling for cell type proportion. EWAS utilizing cord blood are confounded by cell type proportion. Careful study design including correction for cell type proportion and interpretation of results of EWAS using cord blood are critical.