基因型与产前应激对DNA甲基化在出生时的交互影响
Rosa H Mulder1,2, Vilte Baltramonaityte3, Serena Defina1,2
1Department of Adolescent and Child Psychiatry and Psychology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Molecular psychiatry
|October 24, 2025
概括
母亲产前压力与孩子的基因相互作用,影响出生时的DNA甲基化 (DNAm),特别是影响参与神经元发育的基因. 仅仅遗传因素就显示了更多的DNAm关联,而不是基因与环境的相互作用.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 发展生物学 发展生物学
- 遗传学 遗传学 是一个
背景情况:
- 宫内压力暴露会影响后代的健康,DNA甲基化 (DNAm) 被认为是关键机制.
- 以前的研究发现产前压力和DNAm之间存在有限的关联,这表明存在复杂的相互作用.
- 新出现的证据表明,基因环境相互作用比单独的任何一个因素更好地预测DNAm.
研究的目的:
- 调查与基因变异相互作用的孕产前压力是否与出生时的DNA甲基化 (DNAm) 有关.
- 为了探索全基因组DNAm.m.的全基因组基因型-产前压力相互作用 (GxE).
- 将GxE模型与仅考虑遗传变异 (Gmodel) 或产前压力 (Emodel) 的模型进行比较.
主要方法:
- 对2963对母婴对进行分析,这些对来自R世代研究和Avon长度研究的父母和孩子.
- 使用了一种协调的,全面的累积产前压力测量方法.
- 在DNAm上测试了全基因组基因型-由-产前压力相互作用,以及G和E模型.
主要成果:
- 确定了DNAm上两种独立的基因与产前压力相互作用,涉及CHD2,ORC5和EPPK1.1中DNAm位点的变异.
- 相比之下,Gmodel显示了691,202个关联,Emodel显示了三个关联 (AHRR,GFI1,MYO1G),主要是由产前吸烟解释的.
- 与暗示GxE结果相关的基因经常与神经元发育有关.
结论:
- 产前压力与孩子的基因组相互作用,影响与神经元发育相关的基因的DNA甲基化.
- 基因对出生时DNA甲基化的主要影响明显比基因对产前压力相互作用更为普遍.
- 这些发现突出了早期发育过程中遗传学,环境和表观遗传学之间的复杂相互作用.
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