ABSTRACT

Background: We investigated the association between prenatal GDM exposure and offspring DNA methylation (DNAm) age at 3–10 years of age in the Tianjin GDM Observational Study.

Methods: This study included 578 GDM and 578 non-GDM mother-child pairs. Children underwent an exam with anthropometric measurements and blood draw for DNAm analysis (Illumina 850 K array) at a median age of 5.9 years (range 3.1–10.2). DNAm age was calculated using two epigenetic clock algorithms (Horvath and Hannum). The residual resulting from regressing DNAm age on chronological age was used as a metric for age acceleration.

Results: Chronological age was positively correlated with Horvath DNAm age (r = 0.53, p < 0.0001) and Hannum DNAm age (r = 0.38, p < 0.0001). Offspring age acceleration was higher in the GDM group than non-GDM group after adjustment for potential confounders (Horvath: 4.96 months higher, adjusted for sex, pre-pregnancy BMI, cell-type proportions, and technical bias, p = 0.0002; Hannum: 11.2 months higher, adjusted for cell-type proportions and technical bias, p < 0.0001). Increased offspring DNAm age acceleration was associated with increased offspring weight-for-age Z-score, BMI-for-age-Z-score, waist circumference, body fat percentage, subscapular skinfold, suprailiac skinfold, upper-arm circumference, and blood pressure; findings were stronger in the GDM group.

Conclusions: We found that offspring of women with GDM exhibit accelerated epigenetic age compared to control participants, independent of other maternal factors. Epigenetic age in offspring was associated with cardiometabolic risk factors, suggesting that GDM and GDM-associated factors may have long-term effects on offspring epigenetic age and contribute to health outcomes.

摘要

背景：我们在天津 GDM 观察研究中调查了产前 GDM 暴露与后代 3-10 岁 DNA 甲基化 (DNAm) 年龄之间的关联。

方法：本研究包括 578 对 GDM 和 578 对非 GDM 母子。儿童接受人体测量检查和抽血进行 DNAm 分析（Illumina 850 K 阵列），中位年龄为 5.9 岁（范围 3.1-10.2）。DNAm 年龄使用两种表观遗传时钟算法（Horvath 和 Hannum）计算。将 DNAm 年龄回归实际年龄所得的残差用作年龄加速的指标。

结果：实足年龄与 Horvath DNAm 年龄（r = 0.53，p < 0.0001）和 Hannum DNAm 年龄（r = 0.38，p < 0.0001）呈正相关。调整潜在混杂因素后，GDM 组的后代年龄加速高于非 GDM 组（Horvath：高出 4.96 个月，根据性别、孕前 BMI、细胞类型比例和技术偏差进行调整，p = 0.0002；Hannum：提高了 11.2 个月，根据细胞类型比例和技术偏差进行调整，p < 0.0001）。后代 DNAm 年龄加速增加与后代年龄别体重 Z 分数、年龄别体重指数 Z 分数、腰围、体脂百分比、肩胛下皮褶、肩胛上皮褶、上臂周长和血压增加相关; GDM 组的研究结果更为明显。

结论：我们发现，与对照组参与者相比，患有 GDM 的女性的后代表现出更快的表观遗传年龄，而与其他母亲因素无关。后代的表观遗传年龄与心脏代谢危险因素相关，表明 GDM 和 GDM 相关因素可能对后代表观遗传年龄产生长期影响，并有助于健康结果。