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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
DNA methylation profiles in adults born at extremely low birth weight
Karen J Mathewson1, Patrick O McGowan2, Wilfred C de Vega2
1Department of Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, ON, Canada.
Insights
Extremely preterm birth may alter DNA methylation patterns, especially in males, impacting genes related to brain development and metabolism. These epigenetic changes highlight sex-specific long-term effects of extreme prematurity.
Area of Science:
- Epigenetics
- Genomics
- Developmental Biology
Background:
- Extreme preterm birth can leave lasting biological marks.
- DNA methylation (DNAm) patterns may record early life stress.
- Epigenetic changes can influence long-term health outcomes.
Purpose of the Study:
- To investigate genome-wide DNA methylation differences in adults born extremely preterm versus normal birth weight.
- To explore potential sex differences in epigenetic responses to extreme preterm birth.
- To identify biological pathways affected by these epigenetic modifications.
Main Methods:
- Genome-wide DNA methylation profiling in buccal cells.
- Comparison of DNAm profiles between extremely low birth weight (ELBW) survivors and normal birth weight (NBW) controls.
- Gene ontology and network analyses to interpret affected genes.
Main Results:
- Sex differences in DNAm were significantly amplified in the ELBW group compared to the NBW group.
- In men, 1,354 DNAm loci across 694 genes differed between ELBW and NBW groups.
- In women, only two DNAm loci on two genes differed between the groups.
- Affected genes in ELBW men were enriched in pathways for neuronal development, synaptic transport, and metabolic regulation.
Conclusions:
- Adults born extremely preterm exhibit distinct DNA methylation profiles, particularly males.
- Males appear more sensitive to the long-term epigenetic effects of extreme prematurity.
- These findings suggest synergistic impacts of prenatal adversity and sex on adult epigenomes.
Abstract:
Effects of stresses associated with extremely preterm birth may be biologically "recorded" in the genomes of individuals born preterm via changes in DNA methylation (DNAm) patterns. Genome-wide DNAm profiles were examined in buccal epithelial cells from 45 adults born at extremely low birth weight (ELBW; ≤1000 g) in the oldest known cohort of prospectively followed ELBW survivors (Mage = 32.35 years, 17 male), and 47 normal birth weight (NBW; ≥2500 g) control adults (Mage = 32.43 years, 20 male). Sex differences in DNAm profiles were found in both birth weight groups, but they were greatly enhanced in the ELBW group (77,895 loci) versus the NBW group (3,424 loci), suggesting synergistic effects of extreme prenatal adversity and sex on adult DNAm profiles. In men, DNAm profiles differed by birth weight group at 1,354 loci on 694 unique genes. Only two loci on two genes distinguished between ELBW and NBW women. Gene ontology (GO) and network analyses indicated that loci differentiating between ELBW and NBW men were abundant in genes within biological pathways related to neuronal development, synaptic transportation, metabolic regulation, and cellular regulation. Findings suggest increased sensitivity of males to long-term epigenetic effects of extremely preterm birth. Group differences are discussed in relation to particular gene functions.
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