Epigenome-Wide Association Study of Infant Feeding and DNA Methylation in Infancy and Childhood in a Population at Increased Risk for Type 1 Diabetes

We assessed associations between infant diet (e.g., breastfeeding and introduction to solid foods) and DNA methylation in infancy and childhood. We measured DNA methylation in peripheral blood collected in infancy (9-15 months of age) in 243 children; and in a subset of 50 children, we also measured methylation in childhood (6-9 years of age) to examine persistence, and at birth (in cord blood) to examine temporality. We performed multivariable linear regression of infant diet on the outcome of methylation using epigenome-wide and candidate site approaches. We identified six novel CpG sites associated with breastfeeding duration using an EWAS approach. One differentially methylated site presented directionally consistent associations with breastfeeding (cg00574958, CPT1A) in infancy and childhood but not at birth. Two differentially methylated sites in infancy (cg19693031, TXNIP; cg23307264, KHSRP) were associated with breastfeeding and were not present at birth; however, these associations did not persist into childhood. Associations between infant diet and methylation in infancy at three sites (cg22369607, AP001525.1; cg2409200, TBCD; cg27173510, PGBD5) were also present at birth, suggesting the influence of exposures other than infant diet. Infant diet exposures are associated with persistent methylation differences in CPT1A, which may be one mechanism behind infant diet's long-term health effects.