胎盘硒相关的DNA甲基化修饰与新生儿神经行为发育：对两个美国出生队列的全表观基因组研究
Selenium-associated DNA methylation modifications in placenta and neurobehavioral development of newborns: An epigenome-wide study of two U.S. birth cohorts.
作者信息
Tian Fu-Ying, Everson Todd M, Lester Barry, Punshon Tracy, Jackson Brian P, Hao Ke, Lesseur Corina, Chen Jia, Karagas Margaret R, Marsit Carmen J
机构信息
Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Brown Center for the Study of Children at Risk, Women and Infants Hospital, Warren Alpert School of Medicine of Brown University, Providence, RI, USA.
出版信息
Environ Int. 2020 Apr;137:105508. doi: 10.1016/j.envint.2020.105508. Epub 2020 Jan 31.
BACKGROUND/AIM: Selenium (Se) levels in pregnancy have been linked to neurobehavioral development of the offspring. DNA methylation is a potential mechanism underlying the impacts of environmental exposures on fetal development; however, very few studies have been done elucidating the role of DNA methylation linking prenatal Se and child neurobehavior. We aimed to investigate the associations between placental Se concentration and epigenome-wide DNA methylation in two U.S. cohorts, and to assess the association between Se-related DNA methylation modifications and newborns' neurobehavior.
METHODS
We measured placental Se concentrations in 343 newborns enrolled in the New Hampshire Birth Cohort Study and in 141 newborns in the Rhode Island Child Health Study. Genome-wide placental DNA methylation was measured by HumanMethylation450 BeadChip, and newborn neurobehavioral development was assessed by the NICU Network Neurobehavioral Scales (NNNS). We meta-analyzed the associations between placental Se concentration and DNA methylation in each cohort, adjusting for covariates. We also fit multiple linear regression and ordinal logistic regression for methylation and newborn NNNS summary scores.
RESULTS
We identified five Se-related differentially methylated CpG sites. Among them was cg09674502 (GFI1), where selenium concentration was positively associated with methylation (β-coefficient = 1.11, FDR-adjusted p-value = 0.045), and where we observed that a one percent methylation level increase was associated with a 15% reduced odds of higher muscle tone in the arms, legs and trunk of newborns, (OR [95% Confidence Interval, CI] = 0.85 [0.77, 0.95]). We also observed for each interquartile range (IQR) increase in selenium concentration in the placenta, there was 1.76 times greater odds of higher hypotonicity (OR [95% CI] = 1.76 [1.12, 2.82]).
CONCLUSIONS
Placental selenium concentration was inversely associated with muscle tone of newborns, and hypermethylation of GFI1 could be a potential mechanism underlying this association.
背景/目的：孕期硒（Se）水平与后代的神经行为发育有关。DNA甲基化是环境暴露影响胎儿发育的潜在机制；然而，很少有研究阐明DNA甲基化在产前硒与儿童神经行为之间的作用。我们旨在调查美国两个队列中胎盘硒浓度与全基因组DNA甲基化之间的关联，并评估与硒相关的DNA甲基化修饰与新生儿神经行为之间的关联。
方法
我们测量了新罕布什尔州出生队列研究中343名新生儿以及罗德岛儿童健康研究中141名新生儿的胎盘硒浓度。通过HumanMethylation450 BeadChip测量全基因组胎盘DNA甲基化，并通过新生儿重症监护病房网络神经行为量表（NNNS）评估新生儿神经行为发育。我们对每个队列中胎盘硒浓度与DNA甲基化之间的关联进行了荟萃分析，并对协变量进行了调整。我们还对甲基化和新生儿NNNS汇总评分进行了多元线性回归和有序逻辑回归分析。
结果
我们确定了5个与硒相关的差异甲基化CpG位点。其中包括cg09674502（GFI1），硒浓度与甲基化呈正相关（β系数 = 1.11，FDR校正p值 = 0.045），我们观察到甲基化水平每增加1%，新生儿手臂、腿部和躯干肌肉张力较高的几率降低15%（OR [95%置信区间，CI] = 0.85 [0.77, 0.95]）。我们还观察到，胎盘硒浓度每增加一个四分位数间距（IQR），肌张力减退较高的几率就会增加1.76倍（OR [95% CI] = 1.76 [1.12, 2.82]）。
结论
胎盘硒浓度与新生儿肌肉张力呈负相关，GFI1的高甲基化可能是这种关联的潜在机制。
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