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Sample Preparation to Bioinformatics Analysis of DNA Methylation: Association Strategy for Obesity and Related Trait Studies
Published on: May 6, 2022
Association of cord blood methylation with neonatal leptin: An epigenome wide association study
Rachel Kadakia1, Yinan Zheng2, Zhou Zhang2
1Division of Endocrinology, Ann and Robert H. Lurie Children's Hospital of Chicago and Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
Insights
Epigenetic changes in newborn blood DNA are linked to leptin levels, a marker of neonatal adiposity. This research explores early life obesity risk factors and potential epigenetic influences on infant body composition.
Area of Science:
- Epigenetics and Developmental Origins of Health and Disease (DOHaD)
- Metabolic Health and Obesity Research
- Neonatal and Pediatric Endocrinology
Background:
- Neonatal adiposity is a significant risk factor for developing childhood obesity.
- Understanding early life influences on adiposity is crucial for obesity prevention strategies.
- Epigenetic modifications in metabolic genes within cord blood may play a role in neonatal adiposity.
Purpose of the Study:
- To investigate the association between cord blood DNA methylation patterns and neonatal adiposity markers.
- To explore the relationship between epigenome-wide DNA methylation and cord blood leptin levels.
- To identify specific genes and differentially methylated regions linked to neonatal body composition.
Main Methods:
- Cross-sectional study of 114 full-term neonates.
- Analysis of cord blood DNA methylation using the Illumina 450K platform.
- Measurement of neonatal body composition via air displacement plethysmography and assessment of cord blood leptin.
- Multivariable linear regression and false discovery rate estimation to identify associations.
Main Results:
- 247 CpG sites and 18 differentially methylated gene regions were significantly associated with cord blood leptin levels.
- No significant associations were found between epigenetic changes and birth weight, fat mass, or percent body fat.
- Key genes identified include DNAJA4, TFR2, SMAD3, PLAG1, FGF1, and HNF4A.
Conclusions:
- Cord blood DNA methylation patterns are associated with cord blood leptin levels, a key indicator of neonatal adiposity.
- These findings suggest a potential role for epigenetics in early life obesity risk.
- Further research can explore the causal pathways linking epigenetic modifications to neonatal adiposity.
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.
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