A meta-analysis of epigenome-wide association studies of ultra-processed food consumption with DNA methylation in European children.

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• Dietary patterns during childhood may interact with biological processes related to health, but more research is needed to understand this relationship.

• Higher consumption of UPFs in children was linked to small changes in DNA methylation, a biological process that helps regulate how genes function.

• These findings highlight growing scientific interest in how diet quality during childhood may influence long-term health.

Introduction

This study aimed to evaluate the association between ultra-processed food (UPF) consumption and differential DNA methylation in blood among European school-aged children (5 to 11 years).

Methods

This was a meta-analysis of epigenome-wide association studies (EWAS) combining data from four studies comprising nine longitudinal birth cohorts. Children with available data on UPF intake and whole-blood DNA methylation were included. UPF consumption, covariates, and DNA methylation were assessed at the same time point, resulting in a cross-sectional analysis. DNA methylation was measured using Illumina arrays, and cohort-specific EWAS results were combined using fixed-effects meta-analysis.

Results 

• Genomic inflation factors ranged from 0.97–1.01 across cohorts and meta-analysis, indicating minimal p-value inflation.

• No cytosine-phosphate-guanine (CpG) reached false discovery rate (FDR) significance (FDR-adjusted p>0.05) for association with UPF intake.

• Four CpGs reached suggestive significance (p<1×10⁻⁵) with low heterogeneity (I²<50%) and consistent direction of effect across cohorts.

• No statistically significant (FDR-adjusted p>0.05) or suggestive (p<1×10⁻⁵) differentially methylated regions (DMRs) were identified.

• In European ancestry–restricted analyses (n=3007), effect estimates were similar; effect size was slightly stronger for cg18968409, and three additional CpGs (cg09709951 [ATF7], cg03999434, cg03041696) met the suggestive threshold (p<1×10⁻⁵).

• After additional adjustment for fruit and vegetable intake, four CpGs remained suggestively associated (including cg18968409 and cg09709951).

• No enriched Gene Ontology (GO) or Kyoto Encyclopaedia of Genes, Genomes (KEGG) pathways survived FDR correction; nominal (p<0.05) enrichment involved transcription, thyroid hormone signalling, DNA repair, cancer, amino acid and energy metabolism.

• No significant enrichment was observed for specific tissues or chromatin states

Conclusion

The study did not identify any CpG sites significantly associated with UPF consumption after correction for multiple testing. However, seven CpG sites showed suggestive associations, indicating potential but inconclusive links between UPF intake and DNA methylation in children.

• The findings highlight the importance of assessing UPF intake when evaluating children’s dietary patterns.

• Practitioners may use these findings to reinforce guidance on improving overall diet quality and limiting UPF consumption during childhood.

• Dietary patterns may influence biological processes involved in gene regulation, highlighting the potential importance of diet quality early in life.

• These insights may support nutrition education and intervention strategies for families, encouraging greater consumption of whole and minimally processed foods in children’s diets.

• Longitudinal or intervention studies are needed to clarify causal relationships between UPF intake and DNA methylation, as the current cross-sectional design limits causal inference.

• Research across broader age groups is warranted, since dietary habits and methylation patterns may change beyond middle childhood (5–11 years).

• Standardised food classification systems may improve comparability across countries where certain foods (e.g., bread) may be classified differently as UPF.

• Studies assessing DNA methylation in tissues beyond blood, including gastrointestinal tissues, may help clarify potential biological mechanisms.