OBJECTIVE Maternal gestational diabetes mellitus (GDM) has been associated with adverse outcomes in the offspring. Growing evidence suggests that the epigenome may play a role, but most previous studies have been small and adjusted for few covariates. The current study meta-analyzed the association between maternal GDM and cord blood DNA methylation in the Pregnancy and Childhood Epigenetics (PACE) consortium. RESEARCH DESIGN AND METHODS Seven pregnancy cohorts (3,677 mother-newborn pairs [317 with GDM]) contributed results from epigenome-wide association studies, using DNA methylation data acquired by the Infinium HumanMethylation450 BeadChip array. Associations between GDM and DNA methylation were examined using robust linear regression, with adjustment for potential confounders. Fixed-effects meta-analyses were performed using METAL. Differentially methylated regions (DMRs) were identified by taking the intersection of results obtained using two regional approaches: comb-p and DMRcate. RESULTS Two DMRs were identified by both comb-p and DMRcate. Both regions were hypomethylated in newborns exposed to GDM in utero compared with control subjects. One DMR (chr 1: 248100345-248100614) was located in the OR2L13 promoter, and the other (chr 10: 135341870-135342620) was located in the gene body of CYP2E1. Individual CpG analyses did not reveal any differentially methylated loci based on a false discovery rate-adjusted P value threshold of 0.05. CONCLUSIONS Maternal GDM was associated with lower cord blood methylation levels within two regions, including the promoter of OR2L13, a gene associated with autism spectrum disorder, and the gene body of CYP2E1, which is upregulated in type 1 and type 2 diabetes. Future studies are needed to understand whether these associations are causal and possible health consequences.

中文翻译：

---

孕产妇妊娠糖尿病和新生儿 DNA 甲基化：妊娠和儿童表观遗传学联盟的研究结果。

目的 母体妊娠期糖尿病 (GDM) 与后代的不良结局相关。越来越多的证据表明表观基因组可能发挥了作用，但大多数先前的研究规模很小，并且针对少数协变量进行了调整。目前的研究荟萃分析了妊娠和儿童表观遗传学 (PACE) 联盟中母体 GDM 与脐带血 DNA 甲基化之间的关联。研究设 使用稳健的线性回归检查 GDM 和 DNA 甲基化之间的关联，并调整潜在的混杂因素。使用 METAL 进行固定效应荟萃分析。通过使用两种区域方法获得的结果的交集来确定差异甲基化区域 (DMR)：comb-p 和 DMRcate。结果comb-p 和DMRcate 鉴定了两个DMR。与对照组相比，在子宫内暴露于 GDM 的新生儿中，这两个区域的甲基化程度都较低。一个 DMR (chr 1: 248100345-248100614) 位于 OR2L13 启动子中，另一个 (chr 10: 135341870-135342620) 位于 CYP2E1 的基因体中。基于错误发现率调整的 P 值阈值为 0.05，单个 CpG 分析未显示任何差异甲基化基因座。结论 母体 GDM 与两个区域内较低的脐带血甲基化水平相关，包括与自闭症谱系障碍相关的基因 OR2L13 的启动子和 CYP2E1 的基因体，在 1 型和 2 型糖尿病中上调。未来的研究需要了解这些关联是否是因果关系和可能的健康后果。