University of Cincinnati College of Medicine, Department of Environmental and Public Health Sciences, Cincinnati, OH, USA.
Erasmus MC, University Medical Center Rotterdam, Department of Adolescent and Child Psychiatry and Psychology, Rotterdam, Netherlands.
Mol Psychiatry. 2023 Dec;28(12):5090-5100. doi: 10.1038/s41380-023-02010-5. Epub 2023 Mar 10.
Prenatal maternal stressful life events are associated with adverse neurodevelopmental outcomes in offspring. Biological mechanisms underlying these associations are largely unknown, but DNA methylation likely plays a role. This meta-analysis included twelve non-overlapping cohorts from ten independent longitudinal studies (N = 5,496) within the international Pregnancy and Childhood Epigenetics consortium to examine maternal stressful life events during pregnancy and DNA methylation in cord blood. Children whose mothers reported higher levels of cumulative maternal stressful life events during pregnancy exhibited differential methylation of cg26579032 in ALKBH3. Stressor-specific domains of conflict with family/friends, abuse (physical, sexual, and emotional), and death of a close friend/relative were also associated with differential methylation of CpGs in APTX, MyD88, and both UHRF1 and SDCCAG8, respectively; these genes are implicated in neurodegeneration, immune and cellular functions, regulation of global methylation levels, metabolism, and schizophrenia risk. Thus, differences in DNA methylation at these loci may provide novel insights into potential mechanisms of neurodevelopment in offspring.
产前母体应激性生活事件与后代不良神经发育结局相关。这些关联的潜在生物学机制尚不清楚，但 DNA 甲基化可能起作用。本荟萃分析纳入了国际妊娠和儿童表观遗传学联盟中十个独立纵向研究的 12 个非重叠队列（N=5496），旨在探讨妊娠期间母体应激性生活事件与脐带血中 DNA 甲基化的关系。与母亲报告的妊娠期间累积母体应激性生活事件水平较高的儿童相比，ALKBH3 中的 cg26579032 表现出差异甲基化。与家庭/朋友冲突、虐待（身体、性和情感）以及亲密朋友/亲属死亡等应激源特定领域也分别与 APTX、MyD88 以及 UHRF1 和 SDCCAG8 中的 CpG 差异甲基化相关；这些基因与神经退行性变、免疫和细胞功能、全球甲基化水平的调节、代谢以及精神分裂症风险有关。因此，这些基因座的 DNA 甲基化差异可能为后代神经发育的潜在机制提供新的见解。
