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

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. 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. 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. 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.</p

Epigenome–wide Meta–Analysis Reveals Associations between Dietary Glycemic Index and Glycemic Load and DNA methylation in Children and Adolescents with Different Body Size

Objective: Dietary glycemic index (GI) and glycemic load (GL) are associated with cardio–metabolic health in children and adolescents, with potential distinct effects in people with increased body mass index (BMI). DNA methylation (DNAm) may mediate these effects. Thus, we conducted meta–analyses of epigenome–wide association studies (EWASs) between dietary GI and GL and blood DNAm of children and adolescents.Research Design and Methods: We calculated dietary GI and GL and performed EWASs in children and adolescents (age range: 4.5–17 years) from six cohorts (ntotal = 1,187). We performed stratified analyses of participants with normal–weight (ntotal = 801) or overweight/obesity (ntotal = 386). We performed look–ups for the identified cytosine–phosphate–guanine (CpG) sites (false discovery rate (FDR) Results: Dietary GL was positively associated with DNAm of cg20274553 (FDR Conclusions: We identified 537 associations between dietary GI and GL and blood DNAm, mainly in children and adolescents with overweight/obesity. High GI and/or GL diets may influence epigenetic gene regulation and thereby, promote metabolic derangements in young persons with increased BMI.</p