Breastfeeding association with DNA methylation in the pregnancy and childhood epigenetics (PACE) consortium

Breastfeeding is associated with short- and long-term beneficial effects on child health, including greater cognitive development, and enhanced immune programming. However, the underlying biological mechanisms are only partially understood, with epigenetics emerging as a potential contributor. In this study, we aimed to investigate whether breastfeeding practices are associated with differential DNA methylation (DNAm) in childhood blood.

We conducted meta-analyses of epigenome-wide association studies (meta-EWASs) in 3421 children from eleven international population-based birth cohorts from the Pregnancy And Childhood Epigenetics (PACE) Consortium. Breastfeeding was assessed as "ever" being breastfed vs. "never", and duration of any and exclusive breastfeeding. DNAm was measured in childhood blood (ages 5-12 years) using the Illumina 450 K or EPIC arrays, with cord blood at birth used as negative outcome control. At False Discovery Rate (FDR) < 5%, positive associations at six cytosine-phosphate-guanine (CpG) sites were identified in childhood blood: four with duration of exclusive breastfeeding, and three with duration of exclusive breastfeeding of more than three months compared to never. The annotated genes (ALAD, FNBP4, and CHFR) are related to developmental and immune processes. None of these CpG sites were FDR-significant in cord blood prior to breastfeeding.

Breastfeeding was associated with differential DNAm in childhood blood at a limited number of CpG sites. Future studies in diverse populations are needed to examine the robustness of these associations, the sources of heterogeneity, and the generalizability of the findings.