Jami L. Josefson, Alan Kuang, Catherine Allard, Monica E. Bianco, William Lowe Jr., Denise M. Scholtens, Luigi Bouchard, Marie-France Hivert
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引用次数: 0
摘要
目的:本研究旨在确定脐带血 DNA 甲基化是否与新生儿肥胖(儿童肥胖的关键风险因素)有关:本研究旨在确定脐带血DNA特定位点的甲基化是否与新生儿肥胖(儿童肥胖的关键风险因素)有关:以高血糖和不良妊娠结局(HAPO)研究为发现样本,进行了一项表观基因组关联研究。采用线性回归模型,对母体和后代协变量及细胞计数进行调整,分析新生儿脂肪含量(以三个皮褶厚度之和计)与脐带血DNA甲基化之间的关联。检测使用 Illumina EPIC 阵列(质控后有 791,359 个 CpG 位点)进行。在一个独立队列 "妊娠和生长过程中葡萄糖调节的遗传学(Genetics of Glucose regulation in Gestation and Growth,Gen3G)"中进行了复制:结果:在 2740 个 HAPO 样本中,经多重检验后发现 89 个 CpG 位点存在显著关联(Bonferroni-adjusted p 结论):这些研究结果支持表观遗传机制在新生儿肥胖发育起源中的作用,并可作为代谢性疾病风险的潜在生物标志物。
Newborn adiposity is associated with cord blood DNA methylation at IGF1R and KLF7
Objective
This study aimed to identify whether cord blood DNA methylation at specific loci is associated with neonatal adiposity, a key risk factor for childhood obesity.
Methods
An epigenome-wide association study was conducted using the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study as a discovery sample. Linear regression models adjusted for maternal and offspring covariates and cell counts were used to analyze associations between neonatal adiposity as measured by sum of three skinfold thicknesses and cord blood DNA methylation. Assays were performed with Illumina EPIC arrays (791,359 CpG sites after quality control). Replication was performed in an independent cohort, Genetics of Glucose regulation in Gestation and Growth (Gen3G).
Results
In 2740 HAPO samples, significant associations were identified at 89 CpG sites after accounting for multiple testing (Bonferroni-adjusted p < 0.05). Replication analyses conducted in 139 Gen3G participants confirmed associations for seven CpG sites. These included IGF1R, which encodes a transmembrane receptor involved in cell growth and survival that binds insulin-like growth factor I and insulin, and KLF7, which encodes a regulator of cell proliferation and inhibitor of adipogenesis; both are key regulators of growth during fetal life.
Conclusions
These findings support epigenetic mechanisms in the developmental origins of neonatal adiposity and as potential biomarkers of metabolic disease risk.
期刊介绍:
Obesity is the official journal of The Obesity Society and is the premier source of information for increasing knowledge, fostering translational research from basic to population science, and promoting better treatment for people with obesity. Obesity publishes important peer-reviewed research and cutting-edge reviews, commentaries, and public health and medical developments.