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Association of cord blood methylation with neonatal leptin: An epigenome wide association study.

ABSTRACT: BACKGROUND:Neonatal adiposity is a risk factor for childhood obesity. Investigating contributors to neonatal adiposity is important for understanding early life obesity risk. Epigenetic changes of metabolic genes in cord blood may contribute to excessive neonatal adiposity and subsequent childhood obesity. This study aims to evaluate the association of cord blood DNA methylation patterns with anthropometric measures and cord blood leptin, a biomarker of neonatal adiposity. METHODS:A cross-sectional study was performed on a multiethnic cohort of 114 full term neonates born to mothers without gestational diabetes at a university hospital. Cord blood was assayed for leptin and for epigenome-wide DNA methylation profiles via the Illumina 450K platform. Neonatal body composition was measured by air displacement plethysmography. Multivariable linear regression was used to analyze associations between individual CpG sites as well as differentially methylated regions in cord blood DNA with measures of newborn adiposity including anthropometrics (birth weight, fat mass and percent body fat) and cord blood leptin. False discovery rate was estimated to account for multiple comparisons. RESULTS:247 CpG sites as well as 18 differentially methylated gene regions were associated with cord blood leptin but no epigenetic changes were associated with birth weight, fat mass or percent body fat. Genes of interest identified in this study are DNAJA4, TFR2, SMAD3, PLAG1, FGF1, and HNF4A. CONCLUSION:Epigenetic changes in cord blood DNA are associated with cord blood leptin levels, a measure of neonatal adiposity.

SUBMITTER: Kadakia R

PROVIDER: S-EPMC6919608 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Association of cord blood methylation with neonatal leptin: An epigenome wide association study.

Kadakia Rachel R Zheng Yinan Y Zhang Zhou Z Zhang Wei W Josefson Jami L JL Hou Lifang L

PloS one 20191218 12

<h4>Background</h4>Neonatal adiposity is a risk factor for childhood obesity. Investigating contributors to neonatal adiposity is important for understanding early life obesity risk. Epigenetic changes of metabolic genes in cord blood may contribute to excessive neonatal adiposity and subsequent childhood obesity. This study aims to evaluate the association of cord blood DNA methylation patterns with anthropometric measures and cord blood leptin, a biomarker of neonatal adiposity.<h4>Methods</h4 ...[more]

PMID: 31851703

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Project description:Background Maternal stress before, during and after pregnancy has profound effects on the development and lifelong function of the infant’s neurocognitive development. We hypothesized that the programming of the central nervous system (CNS), hypothalamic–pituitary–adrenal (HPA) axis and autonomic nervous system (ANS) induced by prenatal stress (PS) is reflected in electrophysiological and epigenetic biomarkers. In this study, we aimed to find noninvasive epigenetic biomarkers of PS in the newborn salivary DNA. Results A total of 728 pregnant women were screened for stress exposure using Cohen Perceived Stress Scale (PSS), 164 women were enrolled, and 114 dyads were analyzed. Prenatal Distress Questionnaire (PDQ) was also administered to assess specific pregnancy worries. Transabdominal fetal electrocardiograms (taECG) were recorded to derive coupling between maternal and fetal heart rates resulting in a ‘Fetal Stress Index’ (FSI). Upon delivery, we collected maternal hair strands for cortisol measurements and newborn’s saliva for epigenetic analyses. DNA was extracted from saliva samples, and DNA methylation was measured using EPIC BeadChip array (850 k CpG sites). Linear regression was used to identify associations between PSS/PDQ/FSI/Cortisol and DNA methylation. We found epigenome-wide significant associations for 5 CpG with PDQ and cortisol at FDR < 5%. Three CpGs were annotated to genes (Illumina Gene annotation file): YAP1, TOMM20 and CSMD1, and two CpGs were located approximately lay at 50 kb from SSBP4 and SCAMP1. In addition, two differentiated methylation regions (DMR) related to maternal stress measures PDQ and cortisol were found: DAXX and ARL4D. Conclusions Genes annotated to these CpGs were found to be involved in secretion and transportation, nuclear signaling, Hippo signaling pathways, apoptosis, intracellular trafficking and neuronal signaling. Moreover, some CpGs are annotated to genes related to autism, post-traumatic stress disorder (PTSD) and schizophrenia. However, our results should be viewed as hypothesis generating until replicated in a larger sample. Early assessment of such noninvasive PS biomarkers will allow timelier detection of babies at risk and a more effective allocation of resources for early intervention programs to improve child development. A biomarker-guided early intervention strategy is the first step in the prevention of future health problems, reducing their personal and societal impact. Supplementary Information The online version contains supplementary material available at 10.1186/s13148-022-01310-x.

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Project description:Panic disorder (PD) is considered to be a multifactorial disorder emerging from interactions among multiple genetic and environmental factors. To date, although genetic studies reported several susceptibility genes with PD, few of them were replicated and the pathogenesis of PD remains to be clarified. Epigenetics is considered to play an important role in etiology of complex traits and diseases, and DNA methylation is one of the major forms of epigenetic modifications. In this study, we performed an epigenome-wide association study of PD using DNA methylation arrays so as to investigate the possibility that different levels of DNA methylation might be associated with PD.The DNA methylation levels of CpG sites across the genome were examined with genomic DNA samples (PD, N?=?48, control, N?=?48) extracted from peripheral blood. Methylation arrays were used for the analysis. ? values, which represent the levels of DNA methylation, were normalized via an appropriate pipeline. Then, ? values were converted to M values via the logit transformation for epigenome-wide association study. The relationship between each DNA methylation site and PD was assessed by linear regression analysis with adjustments for the effects of leukocyte subsets.Forty CpG sites showed significant association with PD at 5% FDR correction, though the differences of the DNA methylation levels were relatively small. Most of the significant CpG sites (37/40 CpG sites) were located in or around CpG islands. Many of the significant CpG sites (27/40 CpG sites) were located upstream of genes, and all such CpG sites with the exception of two were hypomethylated in PD subjects. A pathway analysis on the genes annotated to the significant CpG sites identified several pathways, including "positive regulation of lymphocyte activation."Although future studies with larger number of samples are necessary to confirm the small DNA methylation abnormalities associated with PD, there is a possibility that several CpG sites might be associated, together as a group, with PD.

Dataset Information

Association of cord blood methylation with neonatal leptin: An epigenome wide association study.

Publications

Association of cord blood methylation with neonatal leptin: An epigenome wide association study.

Similar Datasets

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