Maternal and Paternal Dietary Quality and Dietary Inflammation Associations with Offspring DNA Methylation and Epigenetic Biomarkers of Aging in the Lifeways Cross-Generation Study

Background: Early-life nutritional exposures may contribute to offspring epigenetic modifications. However, few studies have evaluated parental dietary quality effects on offspring DNA methylation (DNAm).

Objectives: We aim to fill this gap by elucidating the influence of maternal and paternal whole-diet quality and inflammatory potential on offspring DNAm in the Lifeways Cross-generation cohort.

Methods: Families (n = 1124) were recruited around 16 weeks of gestation in the Republic of Ireland between 2001 and 2003. Maternal dietary intake during the first trimester and paternal diet during the 12 previous months were assessed with an FFQ. Parental dietary inflammatory potential and quality were determined using the energy-adjusted Dietary Inflammatory Index (E-DII), the Healthy Eating Index-2015 (HEI-2015), and the maternal DASH score. DNAm in the saliva of 246 children at age nine was measured using the Illumina Infinium HumanMethylationEPIC array. DNAm-derived biomarkers of aging, the Pediatric-Buccal-Epigenetic clock and DNAm estimator of telomere length, were calculated. Parental diet associations with the DNAm concentrations of 850K Cytosine-phosphate-guanine sites (CpG sites) and with DNAm-derived biomarkers of aging were examined using an epigenome-wide association study and linear regressions, respectively.

Results: Maternal HEI-2015 scores were inversely associated with DNAm at CpG site (cg21840035) located near the PLEKHM1 gene, whose functions involve regulation of bone development (β = -0.0036, per 1 point increase in the score; P = 5.6 × 10^-8). Higher paternal HEI-2015 score was related to lower methylation at CpG site (cg22431767), located near cell signaling gene LUZP1 (β = -0.0022, per 1 point increase in the score, P = 4.1 × 10^-8). There were no associations with parental E-DII and DASH scores, and no evidence of major effects on biomarkers of aging.

Conclusions: Parental dietary quality in the prenatal period, evaluated by the HEI-2015, may influence offspring DNAm during childhood. Further research to improve our understanding of parental nutritional programming is warranted.