Maternal anxiety during pregnancy and newborn epigenome-wide DNA methylation

Maternal anxiety during pregnancy is associated with adverse fetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered fetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations between maternal anxiety, measured prospectively during pregnancy, and genome-wide DNAm from umbilical cord blood. Sixteen non-overlapping cohorts from 12 independent longitudinal studies of the Pregnancy And Childhood Epigenetics Consortium participated, resulting in a combined dataset of 7 243 mother-child dyads. We examined prenatal anxiety in relation to genome-wide DNAm and differentially methylated regions. We observed no association between the general symptoms of anxiety during pregnancy or pregnancy-related anxiety, and DNAm at any of the CpG sites, after multiple-testing correction. Further, we identify no differentially methylated regions associated with maternal anxiety. At the cohort-level, of the 21 associations observed in individual cohorts, none replicated consistently in the other cohorts. In conclusion, contrary to some previous studies proposing cord blood DNAm as a promising potential mechanism explaining the link between maternal anxiety during pregnancy and adverse outcomes in offspring, we found no consistent evidence for any robust associations between maternal anxiety and DNAm in cord blood. Larger studies and analysis of DNAm in other tissues may be needed to establish subtle or subgroup-specific associations between maternal anxiety and the fetal epigenome. In this dataset, we present all probe-level summary statistics for one of the two secondary meta-analyses, as described in more detail in the publication (Sammallahti, Cortes Hidalgo, et al, Molecular Psychiatry, in press). We present here the associations between maternal anxiety during pregnancy (general rather than pregnancy-related anxiety; binary variable where 1=high and 0=low anxiety) and cord blood DNA methylation at birth (continuous beta values where 1=completely methylated and 0=completely unmethylated) of <strong>CpG sites that were only present in the Illumina EPIC array</strong> (not on the Illumina 450k array). We adjusted for child sex, maternal socioeconomic class, maternal age, ancestry, batch, and cell counts. The sample size, unadjusted p-value, the z estimate from the sample-size weighted meta-analysis, and the direction of effects across each cohorts are shown. Upload of this dataset was completed by The EWAS Catalog team. The data can be queried along with hundreds of other EWAS at ewascatalog.org. To upload your EWAS summary statistics and have a zenodo DOI generated for you go to ewascatalog.org/upload孕期母亲焦虑与不良胎儿、新生儿及儿童结局密切相关，但其潜在生物学机制尚未明确。胎儿DNA甲基化（DNA methylation, DNAm）异常已被假说为潜在的核心机制之一。本研究通过荟萃分析，探究孕期前瞻性评估的母亲焦虑与脐血全基因组DNA甲基化之间的关联。来自妊娠与儿童表观遗传学联盟（Pregnancy And Childhood Epigenetics Consortium）的12项独立纵向研究中共16个非重叠队列参与了本研究，最终合并得到包含7243对母婴的数据集。本研究分析了产前焦虑与全基因组DNA甲基化及差异甲基化区域（differentially methylated regions, DMRs）的关联。经多重检验校正后，未观察到孕期广泛性焦虑症状或妊娠相关性焦虑与任何CpG位点（CpG sites）的DNA甲基化存在关联。此外，未发现与母亲焦虑相关的差异甲基化区域。在队列层面，单个队列中观察到的21项关联均未在其他队列中得到一致性验证。综上，尽管既往部分研究提出脐血DNA甲基化可作为解释孕期母亲焦虑与子代不良结局之间关联的潜在机制，但本研究未发现孕期母亲焦虑与脐血DNA甲基化存在可靠关联的一致性证据。未来或需开展更大规模的研究，并分析其他组织中的DNA甲基化水平，以明确母亲焦虑与胎儿表观基因组之间是否存在细微或亚组特异性关联。本数据集呈现了两项次级荟萃分析其中一项的所有探针水平汇总统计量，详细说明参见已发表论文（Sammallahti、Cortes Hidalgo等，《分子精神病学（Molecular Psychiatry）》，即将刊出）。本数据集展示了孕期母亲焦虑（广泛性焦虑而非妊娠相关性焦虑；二元变量，1表示高焦虑，0表示低焦虑）与出生时脐血DNA甲基化的关联，其中甲基化水平以连续型β值表示，1代表完全甲基化，0代表完全未甲基化，且分析对象为**仅在Illumina EPIC芯片（而非Illumina 450k芯片）上覆盖的CpG位点**。本研究对儿童性别、母亲社会经济地位、母亲年龄、遗传血统、批次效应及细胞比例进行了校正。数据集包含样本量、未校正p值、基于样本量加权荟萃分析得到的z估计值，以及各队列的效应方向。本数据集由表观基因组全关联研究目录（EWAS Catalog）团队上传。用户可在ewascatalog.org网站查询本数据集及其他数百项表观基因组全关联研究（Epigenome-Wide Association Studies, EWAS）的数据。若需上传您的EWAS汇总统计量并生成Zenodo DOI，请访问ewascatalog.org/upload