脐带血中的 DNA 甲基化变化与健康和疾病的发育起源——系统评价和复制研究。
DNA methylation changes in cord blood and the developmental origins of health and disease - a systematic review and replication study.
机构信息
Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, 237 Barton Street East, Hamilton, ON, Canada.
Department of Medicine, McMaster University, 1280 Main Street West, L8S 4K1, Hamilton, ON, Canada.
出版信息
BMC Genomics. 2022 Mar 19;23(1):221. doi: 10.1186/s12864-022-08451-6.
BACKGROUND
Environmental exposures in utero which modify DNA methylation may have a long-lasting impact on health and disease in offspring. We aimed to identify and replicate previously published genomic loci where DNA methylation changes are attributable to in utero exposures in the NutriGen birth cohort studies Alliance.
METHODS
We reviewed the literature to identify differentially methylated sites of newborn DNA which are associated with the following five traits of interest maternal diabetes, pre-pregnancy body mass index (BMI), diet during pregnancy, smoking, and gestational age. We then attempted to replicate these published associations in the Canadian Healthy Infant Longitudinal Development (CHILD) and the South Asian birth cohort (START) cord blood epigenome-wide data.
RESULTS
We screened 68 full-text articles and identified a total of 17 cord blood epigenome-wide association studies (EWAS) of the traits of interest. Out of the 290 CpG sites reported, 19 were identified in more than one study; all of them associated with maternal smoking. In CHILD and START EWAS, thousands of sites associated with gestational age were identified and maintained significance after correction for multiple testing. In CHILD, there was differential methylation observed for 8 of the published maternal smoking sites. No other traits tested (i.e., folate levels, gestational diabetes, birthweight) replicated in the CHILD or START cohorts.
CONCLUSIONS
Maternal smoking during pregnancy and gestational age are strongly associated with differential methylation in offspring cord blood, as assessed in the EWAS literature and our birth cohorts. There are a limited number of reported methylation sites associated in more than two independent studies related to pregnancy. Additional large studies of diverse populations with fine phenotyping are needed to produce robust epigenome-wide data in order to further elucidate the effect of intrauterine exposures on the infants' methylome.
背景
在子宫内改变 DNA 甲基化的环境暴露可能对后代的健康和疾病产生持久影响。我们旨在确定和复制先前发表的基因组位置，这些位置的 DNA 甲基化变化归因于 NutriGen 出生队列研究联盟中的宫内暴露。
方法
我们查阅文献，以确定与以下五个感兴趣的特征相关的新生儿 DNA 的差异甲基化位点：母亲的糖尿病、孕前体重指数（BMI）、孕期饮食、吸烟和胎龄。然后，我们试图在加拿大健康婴儿纵向发展（CHILD）和南亚出生队列（START）脐带血全基因组范围内的数据中复制这些已发表的关联。
结果
我们筛选了 68 篇全文文章，共确定了 17 项与感兴趣特征相关的脐带血全基因组关联研究（EWAS）。在所报告的 290 个 CpG 位点中，有 19 个在超过一项研究中被发现；所有这些位点都与母亲吸烟有关。在 CHILD 和 START EWAS 中，鉴定了数千个与胎龄相关的位点，在进行多次测试校正后仍保持显著。在 CHILD 中，观察到与 8 个已发表的母亲吸烟位点的差异甲基化。在 CHILD 或 START 队列中没有复制到其他测试的特征（即叶酸水平、妊娠糖尿病、出生体重）。
结论
正如在 EWAS 文献和我们的出生队列中评估的那样，母亲在怀孕期间吸烟和胎龄与后代脐带血中的差异甲基化密切相关。与妊娠相关的独立研究超过两项的报告甲基化位点数量有限。需要对具有精细表型的不同人群进行更多的大型研究，以产生稳健的全基因组数据，从而进一步阐明宫内暴露对婴儿甲基组的影响。
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