Adolescent dietary patterns and methyl-donor nutrient intakes in relation to blood leukocyte DNA methylation of circadian genes

Dietary composition may impact circadian rhythms, potentially through DNA methylation of circadian genes. However, research among adolescents remains limited. Cross-sectional association of three dietary patterns, derived from principal component analysis of energy-adjusted food groups, and five energy-adjusted methyl-donor nutrients (folate, methionine, riboflavin, and vitamins B6 and B12) on DNA methylation of 18 circadian-related genes in 526 adolescents was examined. DNA methylation levels at CpG sites were quantified from blood leukocytes using the Illumina Infinium Methylation EPIC BeadChip, with false discovery rate adjustments (<i>q ≤ 0.20</i>). Linear regression was used, adjusting for age, sex, maternal education, smoking status, batch effects, and cell-type proportions. Correlations between CpG sites and gene expression data (RNA-seq) of the corresponding genes were evaluated. Riboflavin was negatively associated with cg06337557 (<i>MTNR1B</i>) and cg02076826 (<i>RORA</i>). Vitamin B6 was positively associated with cg09615953 (<i>PER3</i>) and negatively with cg06337557 (<i>MTNR1B</i>). In males, the <i>Breakfast</i> pattern was negatively associated with cg13146553 (<i>RORA</i>), and riboflavin was positively associated with cg06487986 (<i>PER3</i>). No significant associations were found for the <i>Plant-based &amp; lean proteins</i> pattern, folate, methionine, or vitamin B12. DNA methylation of the 18 clock genes were not correlated with gene expression data of the corresponding genes. Dietary patterns and methyl-donor nutrients may influence core clock and melatonin-related genes, with potential sex-specific relationships.