Epigenome-Wide Association Study of Mediterranean Diet on Blood DNA Methylation Patterns during Pregnancy: A Pilot Study

Background/Objectives: Consumption of a Mediterranean Diet (MD) has been associated with reduced incidence of non-communicable diseases and reduced overall mortality, with epigenomic effects representing plausible mediators. The aim of this pilot study was to explore potential epigenetic associations between DNA methylation markers in blood and adherence to a MD in pregnancy. Methods: Fifty-two pregnant women with high- or low- adherence to a MD throughout pregnancy, who participated in the Biomood ORI-GINS study, were selected using an extremes of exposure design. DNA methylation (DNAm) profiles from whole blood were generated using the TWIST human methylome panel. We conducted both genome-wide and candidate gene-based differential meth-ylation analyses to identify epigenetic variations between the study groups. Furthermore, we explored potential associations between blood methylation patterns and circulating inflammatory markers (GlycA, GlycB and SPC) previously observed to exhibit differ-ential abundance in the same cohort of women. Results: There were no genome-wide significant differences in methylated dinucleotides between MD groups (p-value < 5e-8), however, 54 CpG dinucleotides met the threshold for a suggestive association with MD adherence. A candidate gene analysis of previously reported MD-associated genes de-tected small but statistically significantly different methylation of CpGs located within COL18A1 and PPARGC1B gene regions. We found statistical evidence of relationships between DNA methylation patterns and SPC inflammatory lipoproteins. Conclusions: We provide preliminary evidence for modest methylation changes in specific genes associated with adherence to MD.