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Comparative Study
. 2021 Mar 19;13(1):57.
doi: 10.1186/s13148-021-01053-1.

Birthweight DNA methylation signatures in infant saliva

Chiara Moccia  1 , Maja Popovic  2 , Elena Isaevska  2 , Valentina Fiano  2 , Morena Trevisan  2 , Franca Rusconi  3 , Silvia Polidoro  4   5 , Lorenzo Richiardi  2
Affiliations
Comparative Study

Birthweight DNA methylation signatures in infant saliva

Chiara Moccia et al. Clin Epigenetics. .

Abstract

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.

Keywords: Birth cohort; Birthweight; Infants; Saliva DNA methylation.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Histogram and qq-plot of the two-sided p-values from the look-up of PACE cord blood findings in infant saliva
Fig. 2
Fig. 2
Volcano plot of the two EWAS. a Volcano plot showing p-values and direction of associations of DNA methylation variation with continuous birthweight. 44 FDR < 0.05 highlighted in red. The blue line is Bonferroni threshold, the red line nominal p-value threshold (p < 0.05). The X-axis represents the % difference in methylation per 100 g in birthweight difference, and the Y-axis represents the − log10(p-value). b Volcano plot showing p-values and direction of associations of DNA methylation variation with AGA vs. SGA. 44 FDR < 0.05 highlighted in red. The blue line is Bonferroni threshold, the red line nominal p-value threshold (p < 0.05).The X-axis represents the % difference in methylation per AGA vs. SGA, and the Y-axis represents the − log10(p-value). In green the CpG that overlap with 44 CpGs on continuous birthweight
See this image and copyright information in PMC

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