Animal and plant protein intake during infancy and childhood DNA methylation: a meta-analysis in the NutriPROGRAM consortium.

BACKGROUND: Higher early-life animal protein intake is associated with a higher childhood obesity risk compared to plant protein intake. Differential DNA methylation may represent an underlying mechanism.

METHODS: We analysed associations of infant animal and plant protein intakes with DNA methylation in early (2-6 years, N  = 579) and late (7̄-12 years, N  = 604) childhood in two studies. Study-specific robust linear regression models adjusted for relevant confounders were run, and then meta-analysed using a fixed-effects model. We also performed sex-stratified meta-analyses. Follow-up analyses included pathway analysis and eQTM look-up.

RESULTS: Infant animal protein intake was not associated with DNA methylation in early childhood, but was associated with late-childhood DNA methylation at cg21300373 ( P  = 4.27 × 10¯8 , MARCHF1 ) and cg10633363 ( P  = 1.09 × 10¯7 , HOXB9 ) after FDR correction. Infant plant protein intake was associated with early-childhood DNA methylation at cg25973293 ( P  = 2.26 × 10-7 , C1orf159 ) and cg15407373 ( P  = 2.13 × 10-7 , MBP ) after FDR correction. There was no overlap between the findings from the animal and plant protein analyses. We did not find enriched functional pathways at either time point using CpGs associated with animal and plant protein. These CpGs were not previously associated with childhood gene expression. Sex-stratified meta-analyses showed sex-specific DNA methylation associations for both animal and plant protein intake.

CONCLUSION: Infant animal protein intake was associated with DNA methylation at two CpGs in late childhood. Infant plant protein intake was associated with DNA methylation in early childhood at two CpGs. A potential mediating role of DNA methylation at these CpGs between infant protein intake and health outcomes requires further investigation.