The environment and events that we are exposed to in utero, during birth and in early childhood influence our future physical and mental health. The underlying mechanisms that lead to these outcomes are unclear, but long-term changes in epigenetic marks, such as DNA methylation, could act as a mediating factor or biomarker. DNA methylation data were assayed at 713 522 CpG sites from 9537 participants of the Generation Scotland: Scottish Family Health Study, a family-based cohort with extensive genetic, medical, family history and lifestyle information. Methylome-wide association studies of eight early life environment phenotypes and two adult mental health phenotypes (major depressive disorder and brief resilience scale) were conducted using DNA methylation data collected from adult whole blood samples. Two genes involved with different developmental pathways (PRICKLE2, Prickle Planar Cell Polarity Protein 2 and ABI1, Abl-Interactor-1) were annotated to CpG sites associated with preterm birth (P < 1.27 × 10−9). A further two genes important to the development of sensory pathways (SOBP, Sine Oculis Binding Protein Homolog and RPGRIP1, Retinitis Pigmentosa GTPase Regulator Interacting Protein) were annotated to sites associated with low birth weight (P < 4.35 × 10−8). The examination of methylation profile scores and genes and gene-sets annotated from associated CpGs sites found no evidence of overlap between the early life environment and mental health conditions. Birth date was associated with a significant difference in estimated lymphocyte and neutrophil counts. Previous studies have shown that early life environments influence the risk of developing mental health disorders later in life; however, this study found no evidence that this is mediated by stable changes to the methylome detectable in peripheral blood.

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早期生活压力源与成人心理健康的全甲基化关联研究

我们在子宫内、出生期间和儿童早期所接触的环境和事件会影响我们未来的身心健康。导致这些结果的潜在机制尚不清楚，但表观遗传标记的长期变化，如 DNA 甲基化，可以作为一个中介因素或生物标志物。DNA 甲基化数据在来自苏格兰一代：苏格兰家庭健康研究的 9537 名参与者的 713 522 个 CpG 位点进行了分析，这是一个以家庭为基础的队列，具有广泛的遗传、医学、家族史和生活方式信息。使用从成人全血样本中收集的 DNA 甲基化数据，对八种早期生活环境表型和两种成人心理健康表型（重度抑郁症和短暂恢复力量表）进行了全甲基化关联研究。涉及不同发育途径的两个基因（PRICKLE2，Prickle Planar Cell Polarity Protein 2 和 ABI1，Abl-Interactor-1）被注释到与早产相关的 CpG 位点（P < 1.27 × 10-9）。另外两个对感觉通路发展很重要的基因（SOBP、Sine Oculis 结合蛋白同源物和 RPGRIP1、视网膜色素变性 GTP 酶调节剂相互作用蛋白）被注释到与低出生体重相关的位点（P < 4.35 × 10-8）。检查甲基化谱评分和从相关 CpGs 位点注释的基因和基因集没有发现早期生活环境和心理健康状况之间重叠的证据。出生日期与估计的淋巴细胞和中性粒细胞计数的显着差异有关。先前的研究表明，早期的生活环境会影响晚年患精神疾病的风险；然而，这项研究没有发现证据表明这是由外周血中可检测到的甲基化组的稳定变化介导的。