# Preliminary Evidence of Blood DNA Methylation Changes in Pregnant Women Adhering to a Mediterranean Diet

## TL;DR

This study found some small changes in blood DNA methylation in pregnant women who followed a Mediterranean diet, linked to genes involved in metabolism and inflammation.

## Contribution

The study provides preliminary evidence of methylation changes in specific genes associated with Mediterranean diet adherence during pregnancy.

## Key findings

- 2210 differentially methylated regions were identified, enriched in metabolic, inflammatory, and neuronal pathways.
- Nine novel DMR associations were replicated using publicly available data.
- Small methylation changes in LPIN1, COL18A1, and PPARGC1B were linked to inflammatory markers and diet adherence.

## Abstract

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 an MD in pregnancy. Methods: Fifty-two pregnant women with high or low adherence to an MD throughout pregnancy, who participated in the BioMood ORIGINS 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 methylation 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 differential abundance in the same cohort of women. Results: There were no genome-wide significant differences in methylated dinucleotides between MD groups (p-value < 5 × 10−8); however, a region-based analysis identified 2210 differentially methylated regions (DMRs) (FDR < 0.05, absolute maximum logFC > 1) annotated to 1537 genes, significantly enriched in metabolic, inflammatory and neuronal signaling pathways. Leveraging publicly available data, we replicated nine novel DMR associations. Changes in circulating phospholipid inflammatory markers were significantly associated with a small methylation difference in Lipin-1 (LPIN1), albeit with a small effect size (p-value < 5 × 10−8). A look-up analysis of previously reported MD-associated genes in this cohort detected small but statistically significantly different methylation of CpGs located within collagen type XVIII alpha 1 (COL18A1) and peroxisome proliferator-activated receptor gamma, coactivator 1 beta (PPARGC1B) gene regions. Conclusions: We provide preliminary evidence for modest methylation changes in specific genes associated with adherence to an MD.