Integrative Analysis of Gene-Specific DNA Methylation and Untargeted Metabolomics Data from the ELEMENT Cohort.

IF 3.2 Q2 GENETICS & HEREDITY
Jaclyn M Goodrich, Emily C Hector, Lu Tang, Jennifer L LaBarre, Dana C Dolinoy, Adriana Mercado-Garcia, Alejandra Cantoral, Peter Xk Song, Martha Maria Téllez-Rojo, Karen E Peterson
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引用次数: 3

Abstract

Epigenetic modifications, such as DNA methylation, influence gene expression and cardiometabolic phenotypes that are manifest in developmental periods in later life, including adolescence. Untargeted metabolomics analysis provide a comprehensive snapshot of physiological processes and metabolism and have been related to DNA methylation in adults, offering insights into the regulatory networks that influence cellular processes. We analyzed the cross-sectional correlation of blood leukocyte DNA methylation with 3758 serum metabolite features (574 of which are identifiable) in 238 children (ages 8-14 years) from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study. Associations between these features and percent DNA methylation in adolescent blood leukocytes at LINE-1 repetitive elements and genes that regulate early life growth (IGF2, H19, HSD11B2) were assessed by mixed effects models, adjusting for sex, age, and puberty status. After false discovery rate correction (FDR q < 0.05), 76 metabolites were significantly associated with LINE-1 DNA methylation, 27 with HSD11B2, 103 with H19, and 4 with IGF2. The ten identifiable metabolites included dicarboxylic fatty acids (five associated with LINE-1 or H19 methylation at q < 0.05) and 1-octadecanoyl-rac-glycerol (q < 0.0001 for association with H19 and q = 0.04 for association with LINE-1). We then assessed the association between these ten known metabolites and adiposity 3 years later. Two metabolites, dicarboxylic fatty acid 17:3 and 5-oxo-7-octenoic acid, were inversely associated with measures of adiposity (P < .05) assessed approximately 3 years later in adolescence. In stratified analyses, sex-specific and puberty-stage specific (Tanner stage = 2 to 5 vs Tanner stage = 1) associations were observed. Most notably, hundreds of statistically significant associations were observed between H19 and LINE-1 DNA methylation and metabolites among children who had initiated puberty. Understanding relationships between subclinical molecular biomarkers (DNA methylation and metabolites) may increase our understanding of genes and biological pathways contributing to metabolic changes that underlie the development of adiposity during adolescence.

Abstract Image

Abstract Image

Abstract Image

来自ELEMENT队列的基因特异性DNA甲基化和非靶向代谢组学数据的综合分析。
表观遗传修饰,如DNA甲基化,影响基因表达和心脏代谢表型,这些表型在包括青春期在内的晚年发育阶段表现出来。非靶向代谢组学分析提供了生理过程和代谢的全面快照,并与成人DNA甲基化有关,为影响细胞过程的调节网络提供了见解。我们分析了来自墨西哥早期生活暴露于环境毒物(ELEMENT)研究的238名儿童(8-14岁)血液白细胞DNA甲基化与3758种血清代谢物特征(其中574种是可识别的)的横断面相关性。这些特征与青少年血液白细胞中LINE-1重复元件和调节早期生命生长的基因(IGF2, H19, HSD11B2) DNA甲基化百分比之间的关联通过混合效应模型进行评估,调整性别,年龄和青春期状态。错误发现率校正(FDR q < 0.05)后,76种代谢物与LINE-1 DNA甲基化显著相关,27种与HSD11B2显著相关,103种与H19显著相关,4种与IGF2显著相关。10种可识别的代谢物包括二羧酸脂肪酸(5种与LINE-1或H19甲基化相关,q < 0.05)和1-十八烷酰丙基甘油(与H19相关,q < 0.0001,与LINE-1相关,q = 0.04)。3年后,我们评估了这10种已知代谢物与肥胖之间的关系。在青春期开始的儿童中,二羧酸17:3和5-氧-7-辛烯酸这两种代谢物与肥胖(ph19和LINE-1 DNA甲基化)和代谢物呈负相关。了解亚临床分子生物标志物(DNA甲基化和代谢物)之间的关系可能会增加我们对促进青春期肥胖发展的代谢变化的基因和生物学途径的理解。
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来源期刊
Epigenetics Insights
Epigenetics Insights GENETICS & HEREDITY-
CiteScore
5.10
自引率
0.00%
发文量
10
审稿时长
8 weeks
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