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Birthweight DNA methylation signatures in infant saliva
Chiara Moccia1, Maja Popovic2, Elena Isaevska2
1Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin and CPO Piemonte, Via Santena 7, 10126, Turin, Italy. chiara.moccia@unito.it.
Insights
Birth weight epigenetic marks in infant saliva differ from cord blood, suggesting they are time and tissue specific. This study identifies saliva-specific DNA methylation signatures for birth weight and small for gestational age in infants.
Area of Science:
- Epigenetics
- Pediatric Health
- Genomics
Background:
- Low birth weight is linked to long-term health issues and non-communicable diseases.
- Understanding birth weight's epigenetic influences is crucial for predicting future health outcomes.
Purpose of the Study:
- To investigate birth weight-associated CpG sites in infant saliva.
- To identify saliva-specific DNA methylation signatures related to birth weight and small for gestational age (SGA).
Main Methods:
- DNA methylation analysis using the Infinium HumanMethylation450K array on 135 infant saliva samples.
- Association analyses between birth weight and DNA methylation using robust linear regression models.
- Exploratory Genome-Wide Association Studies (EWAS) and lookup of existing cord blood data.
Main Results:
- No overlap was found between cord blood birth weight-associated CpGs and infant saliva CpGs.
- Birth weight was associated with 44 CpG sites in infant saliva.
- Small for gestational age (SGA) was associated with 44 different CpG sites, with only one overlap.
Conclusions:
- Saliva DNA methylation signatures for birth weight and SGA were identified in infants around 10 months old.
- Epigenetic marks for birth weight appear to be time and tissue-specific, differing between cord blood and infant saliva.
- Findings suggest that epigenetic signatures of birth weight are dynamic and not universally conserved across tissues and time points.
Background:
Low birthweight has been repeatedly associated with long-term adverse health outcomes and many non-communicable diseases. Our aim was to look-up cord blood birthweight-associated CpG sites identified by the PACE Consortium in infant saliva, and to explore saliva-specific DNA methylation signatures of birthweight.
Methods:
DNA methylation was assessed using Infinium HumanMethylation450K array in 135 saliva samples collected from children of the NINFEA birth cohort at an average age of 10.8 (range 7-17) months. The association analyses between birthweight and DNA methylation variations were carried out using robust linear regression models both in the exploratory EWAS analyses and in the look-up of the PACE findings in infant saliva.
Results:
None of the cord blood birthweight-associated CpGs identified by the PACE Consortium was associated with birthweight when analysed in infant saliva. In saliva EWAS analyses, considering a false discovery rate p-values < 0.05, birthweight as continuous variable was associated with DNA methylation in 44 CpG sites; being born small for gestational age (SGA, lower 10th percentile of birthweight for gestational age according to WHO reference charts) was associated with DNA methylation in 44 CpGs, with only one overlapping CpG between the two analyses. Despite no overlap with PACE results at the CpG level, two of the top saliva birthweight CpGs mapped at genes associated with birthweight with the same direction of the effect also in the PACE Consortium (MACROD1 and RPTOR).
Conclusion:
Our study provides an indication of the birthweight and SGA epigenetic salivary signatures in children around 10 months of age. DNA methylation signatures in cord blood may not be comparable with saliva DNA methylation signatures at about 10 months of age, suggesting that the birthweight epigenetic marks are likely time and tissue specific.
