Adolescent sleep timing and dietary patterns in relation to DNA methylation of core circadian genes: a pilot study of Mexican youth

Abstract

Mistimed sleep/wake and eating patterns put shift workers at increased risk for cardiometabolic disease, and epigenetic modification of circadian genes has been proposed as a mechanism. Although not as extreme as shift workers, adolescents often have delayed sleep timing and irregular eating patterns. The aim was to assess whether sleep midpoints - median of bed and wake time - and dietary patterns in adolescents were associated with DNA methylation of circadian genes. The study population included 142 Mexican youth (average age of 14.0 (SD = 2.0) years, 49% male). Average sleep midpoint over weekdays was estimated with actigraphy. Diet was assessed with a semi-quantitative food frequency questionnaire, and three dietary patterns were derived from principal component analysis, a Plant-based & lean proteins pattern, a Meat & starchy pattern, and an Eggs, milk & refined grain pattern. DNA methylation was quantified in blood leukocytes with the Infinium MethylationEPIC BeadChip, and data from 548 CpG sites within 12 circadian genes were examined. Linear regression analyses, adjusted for sex, age, and % monocytes, showed that later sleep timing was associated with higher DNA methylation of several circadian genes, notably with RORB, PER1, CRY2, and NR1D1. Each of the dietary patterns examined was also related to circadian gene DNA methylation, but the Eggs, milk & refined grain pattern ('breakfast' pattern) had the clearest evidence of relationships with circadian genes, with inverse associations (lower DNA methylation) across all 12 genes. Findings suggest that timing-related sleep and eating behaviours among adolescents could result in epigenetic modification of clock genes.

Keywords: Clock genes; actigraphy; circadian misalignment; epigenetics.