OBJECTIVE Suboptimal nutrition in pregnancy is associated with worse offspring cardiometabolic health. DNA methylation may be an underlying mechanism. We meta-analyzed epigenome-wide association studies (EWAS) of maternal dietary glycemic index and load with cord blood DNA methylation. RESEARCH DESIGN AND METHODS We calculated maternal glycemic index and load from food frequency questionnaires and ran EWAS on cord blood DNA methylation in 2,003 mother-offspring pairs from three cohorts. Analyses were additionally stratified by maternal BMI categories. We looked-up the findings in EWAS of maternal glycemic traits and BMI as well as in EWAS of birth weight and child BMI. We examined associations with gene expression in child blood in the online Human Early Life Exposome eQTM catalog and in 223 adipose tissue samples. RESULTS Maternal glycemic index and load were associated with cord blood DNA methylation at 41 cytosine-phosphate-guanine sites (CpGs, P < 1.17 × 10−7), mostly in mothers with overweight/obesity. We did not observe overlap with CpGs associated with maternal glycemic traits, BMI, or child birth weight or BMI. Only DNA methylation at cg24458009 and cg23347399 was associated with expression of PCED1B and PCDHG, respectively, in child blood, and DNA methylation at cg27193519 was associated with expression of TFAP4, ZNF500, PPL, and ANKS3 in child subcutaneous adipose tissue. CONCLUSIONS We observed multiple associations of maternal glycemic index and load during pregnancy with cord blood DNA methylation, mostly in mothers with overweight/obesity; some of these CpGs were associated with gene expression. Additional studies are required to further explore functionality, uncover causality, and study pathways to offspring health.

中文翻译：

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妊娠期和后代脐带血 DNA 甲基化中的母体膳食血糖指数和血糖负荷

目的 妊娠期营养不良与后代心脏代谢健康状况较差有关。DNA甲基化可能是一个潜在的机制。我们荟萃分析了母体膳食血糖指数和脐带血 DNA 甲基化负荷的表观基因组关联研究 (EWAS)。研究设 分析还按母体 BMI 类别进行分层。我们在 EWAS 中查找了母亲血糖特征和 BMI 以及 EWAS 中关于出生体重和儿童 BMI 的结果。我们检查了在线人类早期生命暴露组 eQTM 目录和 223 个脂肪组织样本中儿童血液中基因表达的关联。结果 母体血糖指数和负荷与脐血 DNA 甲基化在 41 个胞嘧啶-磷酸-鸟嘌呤位点 (CpGs, P < 1.17 × 10-7) 相关，主要发生在超重/肥胖的母亲中。我们没有观察到与母体血糖特征、BMI 或儿童出生体重或 BMI 相关的 CpG 重叠。只有 cg24458009 和 cg23347399 的 DNA 甲基化分别与儿童血液中 PCED1B 和 PCDHG 的表达相关，而 cg27193519 的 DNA 甲基化与儿童皮下脂肪组织中 TFAP4、ZNF500、PPL 和 ANKS3 的表达相关。结 其中一些 CpG 与基因表达有关。