Epigenome-Wide Association Study Reveals Methylation Loci Associated With Offspring Gestational Diabetes Mellitus Exposure and Maternal Methylome.
Epigenome-Wide Association Study Reveals Methylation Loci Associated With Offspring Gestational Diabetes Mellitus Exposure and Maternal Methylome.
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DOI：
10.2337/dc20-2960
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发表时间：
2021-09
期刊：
影响因子：
16.2
通讯作者：
Andrew T
中科院分区：
文献类型：
--
作者：
Canouil M;Khamis A;Keikkala E;Hummel S;Lobbens S;Bonnefond A;Delahaye F;Tzala E;Mustaniemi S;Vääräsmäki M;Jarvelin MR;Sebert S;Kajantie E;Froguel P;Andrew T
妊娠期糖尿病（GDM）与后代日后肥胖和胰岛素抵抗的风险增加有关，这可能是由于母体高血糖暴露引起的表观遗传变化。我们使用Illumina MethylationEPIC 850K BeadChip阵列，在来自前瞻性FinnGeDi队列的536对母子中探索了GDM暴露与母体血液和新生儿脐带血甲基化之间的关联。我们评估了两个假设。首先，我们测试了由GDM暴露引起的共享母体和后代表观遗传效应。其次，我们测试了GDM暴露和母体甲基化是否对后代有表观遗传影响。我们没有发现任何表观遗传标记（差异甲基化的CpG探针）与母亲和后代之间的共享和一致的影响。在模型中包括母体甲基化后，我们在cg22790973探针（TFCP2）上发现了一个与GDM相关的显著（错误发现率为1.38 × 10−2）CpG。我们鉴定了母体甲基化和GDM状态的另外七种FDR显著相互作用，在相同的cg22790973探针（TFCP 2）以及cg03456133、cg24440941（H3C6）、cg20002843（H3C6）处具有最强的关联。（LOC127841）、cg19107264和cg11493553位于UBE3C基因内，cg17065901位于FAM13A内，这两个基因都是2型糖尿病和BMI的易感基因，以及cg23355087位于DLGAP 2基因内，已知其参与妊娠期间的胰岛素抵抗。我们的研究揭示了GDM母亲及其后代之间表观遗传传播的潜在复杂性，这可能不仅取决于GDM暴露，还取决于母体表观遗传状态所指示的其他因素，如母体代谢史。
Gestational diabetes mellitus (GDM) is associated with an increased risk of obesity and insulin resistance in offspring later in life, which might be explained by epigenetic changes in response to maternal hyperglycemic exposure. We explored the association between GDM exposure and maternal blood and newborn cord blood methylation in 536 mother-offspring pairs from the prospective FinnGeDi cohort using Illumina MethylationEPIC 850K BeadChip arrays. We assessed two hypotheses. First, we tested for shared maternal and offspring epigenetic effects resulting from GDM exposure. Second, we tested whether GDM exposure and maternal methylation had an epigenetic effect on the offspring. We did not find any epigenetic marks (differentially methylated CpG probes) with shared and consistent effects between mothers and offspring. After including maternal methylation in the model, we identified a single significant (false discovery rate 1.38 × 10−2) CpG at the cg22790973 probe (TFCP2) associated with GDM. We identified seven additional FDR-significant interactions of maternal methylation and GDM status, with the strongest association at the same cg22790973 probe (TFCP2), as well as cg03456133, cg24440941 (H3C6), cg20002843 (LOC127841), cg19107264, and cg11493553 located within the UBE3C gene and cg17065901 in FAM13A, both susceptibility genes for type 2 diabetes and BMI, and cg23355087 within the DLGAP2 gene, known to be involved in insulin resistance during pregnancy. Our study reveals the potential complexity of the epigenetic transmission between mothers with GDM and their offspring, likely determined by not only GDM exposure but also other factors indicated by maternal epigenetic status, such as maternal metabolic history.
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