Division of Environmental Health Sciences, University of California, Berkeley, CA, USA.
Department of Epidemiology and Population Health, Stanford University School of Medicine, Research Park, 1701 Page Mill Road, Stanford, CA, 94304, USA.
Clin Epigenetics. 2023 Oct 16;15(1):162. doi: 10.1186/s13148-023-01581-y.
Adverse childhood experiences (ACEs) increase the risk of poor health outcomes later in life. Psychosocial stressors may also have intergenerational health effects by which parental ACEs are associated with mental and physical health of children. Epigenetic programming may be one mechanism linking parental ACEs to child health. This study aimed to investigate epigenome-wide associations of maternal preconception ACEs with DNA methylation patterns of children. In the Center for the Health Assessment of Mothers and Children of Salinas study, cord blood DNA methylation was measured using the Illumina HumanMethylation450 BeadChip. Preconception ACEs, which occurred during the mothers' childhoods, were collected using a standard ACE questionnaire including 10 ACE indicators. Maternal ACE exposures were defined in this study as (1) the total number of ACEs; (2) the total number of ACEs categorized as 0, 1-3, and > 4; and (3) individual ACEs. Associations of ACE exposures with differential methylated positions, regions, and CpG modules determined using weighted gene co-expression network analysis were evaluated adjusting for covariates.
Data on maternal ACEs and cord blood DNA methylation were available for 196 mother/newborn pairs. One differential methylated position was associated with maternal experience of emotional abuse (cg05486260/FAM135B gene; q value < 0.05). Five differential methylated regions were significantly associated with the total number of ACEs, and 36 unique differential methylated regions were associated with individual ACEs (Šidák p value < 0.05). Fifteen CpG modules were significantly correlated with the total number of ACEs or individual ACEs, of which 8 remained significant in fully adjusted models (p value < 0.05). Significant modules were enriched for pathways related to neurological and immune development and function.
Maternal ACEs prior to conception were associated with cord blood DNA methylation of offspring at birth. Although there was limited overlap between differential methylated regions and CpGs in modules associated with ACE exposures, statistically significant regions and networks were related to genes involved in neurological and immune function. Findings may provide insights to pathways linking psychosocial stressors to health. Further research is needed to understand the relationship between changes in DNA methylation and child health.
不良的童年经历 (ACEs) 会增加日后健康状况不佳的风险。心理社会压力源也可能通过父母的 ACEs 与儿童的身心健康有关而产生代际健康影响。表观遗传编程可能是将父母 ACEs 与儿童健康联系起来的一种机制。本研究旨在探讨母亲孕前 ACEs 与儿童 DNA 甲基化模式的全基因组关联。在萨利纳斯母婴健康评估中心研究中，使用 Illumina HumanMethylation450 BeadChip 测量脐带血 DNA 甲基化。使用包括 10 个 ACE 指标的标准 ACE 问卷收集母亲童年时期发生的孕前 ACEs。在本研究中，将母亲 ACE 暴露定义为：(1) ACE 总数；(2) 分为 0、1-3 和 >4 的 ACE 总数；(3) 单个 ACE。使用加权基因共表达网络分析评估 ACE 暴露与差异甲基化位置、区域和 CpG 模块之间的关联，调整协变量。
本研究共纳入 196 对母婴。一个差异甲基化位置与母亲遭受情感虐待的经历有关 (cg05486260/FAM135B 基因；q 值<0.05)。5 个差异甲基化区域与 ACE 总数显著相关，36 个独特的差异甲基化区域与单个 ACE 相关 (Šidák p 值<0.05)。15 个 CpG 模块与 ACE 总数或个体 ACE 显著相关，其中 8 个在完全调整模型中仍具有显著意义 (p 值<0.05)。显著模块富含与神经和免疫发育和功能相关的途径。
受孕前母亲 ACEs 与出生时后代脐带血 DNA 甲基化有关。虽然与 ACE 暴露相关的差异甲基化区域和模块中的 CpG 之间存在有限的重叠，但具有统计学意义的区域和网络与涉及神经和免疫功能的基因有关。研究结果可能为将心理社会压力源与健康联系起来的途径提供新的认识。需要进一步研究来了解 DNA 甲基化变化与儿童健康之间的关系。
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