Birthweight DNA Methylation Signatures in Infant Saliva 

Abstract

Background Low birthweight has been repeatedly associated with long-term adverse health outcomes and many non-communicable diseases. Our aim was to investigate whether cord blood birthweight-associated CpG sites identified by the PACE Consortium replicate in infant saliva, and to explore saliva-specific DNA methylation signatures of birthweight. Methods DNA methylation was assessed using Infinium HumanMethylation450K array in 141 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 replication and exploratory EWAS analyses.Results None of the cord blood birthweight-associated CpGs identified by the PACE Consortium was replicated in infant saliva. In saliva EWAS analyses, birthweight as continuous variable was associated with DNA methylation variation in 44 CpG sites, while 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 variation in 44 CpGs (all false discovery rate p-values<0.05), 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 identified also by 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.