产前铅暴露和脐带血DNA甲基化进展:一项全表观基因组关联研究。

IF 4.8 Q1 GENETICS & HEREDITY Environmental Epigenetics Pub Date : 2020-12-08 eCollection Date: 2020-01-01 DOI:10.1093/eep/dvaa014
Jonathan A Heiss, Martha M Téllez-Rojo, Guadalupe Estrada-Gutiérrez, Lourdes Schnaas, Chitra Amarasiriwardena, Andrea A Baccarelli, Robert O Wright, Allan C Just
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引用次数: 8

摘要

产前铅暴露对儿童发育的影响包括生长和认知功能受损。DNA甲基化可能涉及潜在的机制,之前的全表观基因组关联研究报告了妊娠期间铅暴露与脐带血甲基化水平之间的关联。然而,尚不清楚在哪个发育阶段铅暴露是最有害的。使用Illumina Infinium MethylationEPIC微阵列检测来自墨西哥产前队列的420名儿童的脐带血甲基化水平。使用电感耦合血浆质谱法测量脐带血中的铅浓度以及在妊娠第2和第3个月和分娩时收集的母亲的血液样本。此外,利用x射线荧光测定了产妇胫骨和髌骨的骨铅水平。对微阵列数据进行全面的质量控制和预处理,然后对存在较大差异的甲基化位点进行无偏限制。在每次暴露后,对202 - 111个胞嘧啶-磷酸-鸟嘌呤位点的甲基化水平进行回归,调整了儿童性别、白细胞组成、批次变量、胎龄、出生体重/胎龄、母亲年龄、母亲教育程度和分娩方式。我们没有发现产前铅暴露和脐带血甲基化之间的联系。敏感性分析表明,在同一数据集中可以恢复已知的出生体重与胎龄的生物标志物,并且在同一队列中描述了与铅暴露的表型关联,从而加强了这一无效结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Prenatal lead exposure and cord blood DNA methylation in PROGRESS: an epigenome-wide association study.

The effects of prenatal lead exposure on child development include impaired growth and cognitive function. DNA methylation might be involved in the underlying mechanisms and previous epigenome-wide association studies reported associations between lead exposure during pregnancy and cord blood methylation levels. However, it is unclear during which developmental stage lead exposure is most harmful. Cord blood methylation levels were assayed in 420 children from a Mexican pre-birth cohort using the Illumina Infinium MethylationEPIC microarray. Lead concentrations were measured in umbilical cord blood as well as in blood samples from the mothers collected at 2nd and 3rd trimester and delivery using inductively coupled plasma-mass spectrometry. In addition, maternal bone lead levels were measured in tibia and patella using X-ray fluorescence. Comprehensive quality control and preprocessing of microarray data was followed by an unbiased restriction to methylation sites with substantial variance. Methylation levels at 202 111 cytosine-phosphate-guanine sites were regressed on each exposure adjusting for child sex, leukocyte composition, batch variables, gestational age, birthweight-for-gestational-age, maternal age, maternal education and mode of delivery. We find no association between prenatal lead exposure and cord blood methylation. This null result is strengthened by a sensitivity analysis showing that in the same dataset known biomarkers for birthweight-for-gestational-age can be recovered and the fact that phenotypic associations with lead exposure have been described in the same cohort.

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来源期刊
Environmental Epigenetics
Environmental Epigenetics GENETICS & HEREDITY-
CiteScore
6.50
自引率
5.30%
发文量
0
审稿时长
17 weeks
期刊最新文献
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