BC Children's Hospital Research Institute Vancouver, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada.
Dev Psychobiol. 2021 Sep;63(6):e22174. doi: 10.1002/dev.22174. Epub 2021 Aug 1.
Adverse childhood experiences (ACEs), or cumulative childhood stress exposures, such as abuse, neglect, and household dysfunction, predict later health problems in both the exposed individuals and their offspring. One potential explanation suggests exposure to early adversity predicts epigenetic modification, especially DNA methylation (DNAm), linked to later health. Stress experienced preconception by mothers may associate with DNAm in the next generation. We hypothesized that fathers' exposure to ACEs also associates with their offspring DNAm, which, to our knowledge, has not been previously explored. An epigenome-wide association study (EWAS) of blood DNAm (n = 45) from 3-month-old infants was regressed onto fathers' retrospective ACEs at multiple Cytosine-phosphate-Guanosine (CpG) sites to discover associations. This accounted for infants' sex, age, ethnicity, cell type proportion, and genetic variability. Higher ACE scores associated with methylation values at eight CpGs. Post-hoc analysis found no contribution of paternal education, income, marital status, and parental postpartum depression, but did with paternal smoking and BMI along with infant sleep latency. These same CpGs also contributed to the association between paternal ACEs and offspring attention problems at 3 years. Collectively, these findings suggested there were biological associations with paternal early life adversity and offspring DNAm in infancy, potentially affecting offspring later childhood outcomes.
不良的童年经历(ACEs),或累积的童年压力暴露,如虐待、忽视和家庭功能障碍,预测暴露个体及其后代以后的健康问题。一种潜在的解释表明,早期逆境暴露预测了与后来健康相关的表观遗传修饰,特别是 DNA 甲基化(DNAm)。母亲在受孕前经历的压力可能与下一代的 DNAm 相关。我们假设父亲暴露于 ACEs 也与他们的后代的 DNAm 相关,据我们所知,这一点以前尚未被探索过。对来自 3 个月大婴儿的血液 DNAm(n=45)进行了全基因组关联研究(EWAS),以在多个胞嘧啶-磷酸-鸟嘌呤(CpG)位点将父亲的回溯 ACEs 回归到 DNAm 上,以发现关联。这考虑到了婴儿的性别、年龄、种族、细胞类型比例和遗传变异性。较高的 ACE 评分与八个 CpG 处的甲基化值相关。事后分析发现,父亲的教育程度、收入、婚姻状况和产后抑郁与婴儿的睡眠潜伏期没有贡献,但与父亲的吸烟和 BMI 以及婴儿的睡眠潜伏期有贡献。同样的 CpGs 也有助于父亲 ACEs 与 3 岁儿童注意力问题之间的关联。总的来说,这些发现表明,父亲早期生活逆境与婴儿期后代的 DNAm 之间存在生物学关联,可能会影响后代以后的儿童期结局。