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) < 0.05) with tissue–specific gene expression of 832 blood and 223 subcutaneous adipose tissue samples of children and adolescents.

Results: Dietary GL was positively associated with DNAm of cg20274553 (FDR < 0.05), annotated to WDR27. Several CpGs were identified in the normal–weight (GI: 85, GL: 17) and overweight/obese strata (GI: 136, GL: 298; FDR < 0.05), of which none overlapped between the strata. In participants with overweight/obesity, identified CpGs showed relations to RNA expression of genes associated with impaired metabolism, e.g., FRAT1 and CSF3.

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.