背景:不良生活事件对身心健康的影响,以DNA甲基化(DNAm)为关键的潜在机制,已被广泛研究。然而,在忽视照顾的背景下,母亲和孩子之间的表观遗传相似性,以及是否可能由母亲压力事件的情绪影响和共同居住的持续时间(按儿童年龄索引)形成,仍然未知。本研究检查了甲基化谱中的母婴相似性,考虑到逆境母亲的潜在影响,母亲同情,忽视控制组,儿童年龄(母子共同居住年限的指标),和母亲的年龄。使用IlluminaEpic数组,我们对115份母婴唾液样本中的DNAm进行了定量.我们通过计算二元体内甲基化谱之间的相关系数获得了甲基化相似性指数,对于整个表观基因组,和五个与压力和移情相关的特定基因:NR3C1,FKPB5,OXTR,SCL6A4和BDNF。
结果:与整个表观基因组和NR3C1、FKBP5、OXTR和BDNF基因的母子随机对相比,母子家族对的甲基化谱显著相关。接下来,多元线性回归模型观察到母亲逆境的关联,儿童年龄,忽略控制组对母子甲基化相似性,只有在母子家庭对中才有意义,在校正多次比较后。在全基因组分析中,较高的母亲逆境与较低的母子甲基化相似性相关。对于BDNF基因,以及OXTR基因的忽视对照组。反过来,年龄较大的孩子(共同居住时间较长)与较高的母子甲基化相似性相关。
结论:母亲逆境和共同停留时间是代际甲基化过程中的调节因素,为发育依赖性适应提供了一个窗口,这些适应可能受到遗传和环境因素的影响。仅在生物二元体中观察到显著。对儿童福祉有双重含义,一个是积极的,因为母亲的孩子暴露于生活逆境或忽视不一定继承了他们的甲基化模式。另一个是由于一起生活的时间的影响,这会影响与母亲的相似性,并可能增加遗传与未来功能失调的育儿模式相关的表观遗传特征的风险。这强调了\'早期的重要性,儿童保护系统提出的更好的建议,这并不总是遵循。
The effects of adverse life events on physical and psychological health, with DNA methylation (DNAm) as a critical underlying mechanism, have been extensively studied. However, the epigenetic resemblance between mother and child in the context of neglectful caregiving, and whether it may be shaped by the emotional impact of maternal stressful events and the duration of co-residence (indexed by child age), remains unknown. The present study examined mother-child similarity in methylation profiles, considering the potential effect of mother adversity, mother empathy, neglect-control group, child age (an index of years of mother-child co-residence), and mother age. Using Illumina Epic arrays, we quantified DNAm in 115 mother-child saliva samples. We obtained a methylation similarity index by computing correlation coefficients between methylation profiles within dyads, for the entire epigenome, and five specific genes related to stress and empathy: NR3C1, FKPB5, OXTR, SCL6A4, and BDNF.
The methylation profiles of the mother-child familial pairs significantly correlated as compared to mother-child random pairs for the entire epigenome and NR3C1, FKBP5, OXTR and BDNF genes. Next, multiple linear regression models observed associations of mother adversity, child age, and neglect-control group on mother-child methylation similarity, only significant in mother-child familial pairs, after correcting for multiple comparisons. Higher mother adversity was associated with lower mother-child methylation similarity for the epigenome-wide analysis, for the BDNF gene, and in the neglect-control group for the OXTR gene. In turn, being an older child (longer co-residence) was associated with higher mother-child methylation similarity.
Mother adversity and co-residence time are modulating factors in the intergenerational methylation process that offer a window into development-dependent adaptations that can be affected by both hereditary and environmental factors, significantly observed only in biological dyads. A twofold implication for child well-being emerges, one is positive in that children of mothers exposed to life adversity or neglect did not necessarily inherit their methylation patterns. The other is concerning due to the influence of time spent living together, which affects similarity with the mother and potentially increases the risk of inheriting an epigenetic profile associated with future dysfunctional parenting patterns. This underscores the importance of the \'the earlier, the better\' recommendation by the Child Protection System, which is not always followed.