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Nutrition/Obesity

Adolescent dietary patterns in relation to blood leukocyte DNA methylation of circadian genes Jennifer T. Lee* Jennifer Lee Jaclyn M. Goodrich Dana C. Colinoy Karen E. Peterson Martha Maria Tellez-Rojo Alejandra Cantoral Libni Olascoaga-Torres Edward A. Ruiz-Narvaez Erica C. Jansen

Background:

The circadian rhythm, regulated by circadian genes, is involved in multiple metabolic processes and is responsive to diet. The epigenetic modification of DNA methylation (DNAm) is a potential mechanism through which dietary patterns impact health by altering the circadian gene regulation.

Methods:

We conducted secondary cross-sectional analysis of adolescents from the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) cohort. Dietary intake assessed from a semi-quantitative food frequency questionnaire, three dietary patterns were derived using principal component analysis. Blood leukocytes DNAm was measured with Infinium MethylationEPIC BeadChip to obtain data from 707 CpG sites from 18 circadian genes. Linear regression models was used to examine associations between dietary patterns and circadian genes DNAm, adjusted for age, sex, socioeconomic status, batch effects, and estimated blood cell proportions. A 20% false discovery rate using the Benjamini-Hochberg method was applied to correct for multiple testing. Sex-stratified associations were examined. The Cauchy test (ACAT) was used to assess gene-specific associations.

Results:

Sample included 246 males and 277 females (14.50±2.12 years). A Meat & starchy foods pattern was positively associated with a CpG site, cg19170589, within a CpG island of RORA (β=5.31e-3, 95% CI 2.46e-3 to 8.15e-3, q=0.194). An Eggs, milk & refined grain (“breakfast”) pattern was negatively associated with cg13146553 in the gene body of RORA (β=-5.20e-3, 95% CI -7.76e-3 to -2.64e-3, q=0.061) in males. No associations were found with the Plant-based & lean proteins pattern. The ACAT showed significance between Meat & starchy foods pattern with CLOCK (p=0.034), and “breakfast” pattern with NPAS4 (p=0.015).

Conclusion:

Findings suggest dietary patterns among adolescents could result in epigenetic modification of circadian genes, particularly in RORA. Future research may explore the association in a longitudinal design.