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

Abstract

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.

Keywords: DNA methylation; Dietary Inflammatory Index (DII); Healthy-Eating Index (HEI); epigenetic biomarkers of aging; parental dietary quality.

FIGURE 1

Flow-chart of population selection, Lifeways Cross-Generation Cohort Study, Dublin and Galway, Ireland, 2001–2012.

FIGURE 2

Manhattan plot of epigenome-wide association results in offspring associated with the maternal (A) and paternal (B) Healthy Eating Index-2015. The red dashed line represents Bonferroni correction significance threshold (P = 6.3 × 10⁻⁸). The direction of the associations is reported with negative effects below zero and positive effects above zero. Model adjusted for batch effect, child sex, maternal or paternal smoking, and cellular composition.

FIGURE 3

Scatterplots of the comparison of the maternal and paternal dietary associations with individual CpG sites in the Lifeways Cross-Generation Cohort Study. (A) Selection of the top 50 CpG sites associated with the maternal Healthy Eating Index (HEI)-2015, and comparison with the paternal HEI-2015 effects on these CpG sites. (B) Selection of the top 50 CpG sites associated with the paternal HEI-2015, and comparison with the maternal HEI-2015 effects on these CpG sites. (C) Selection of the top 50 CpG sites associated with the maternal energy-adjusted Dietary Inflammatory Index (E-DII), and comparison with the paternal E-DII effects on these CpG sites. (D) Selection of the top 50 CpG sites associated with the paternal E-DII, and comparison with the maternal E-DII effects on these CpG sites. Models adjusted for batch effect, child sex, paternal smoking or maternal smoking, and cellular composition. E-DII, energy-adjusted dietary inflammatory index; HEI, healthy eating index.

Fig. S1

A scatterplot with regression line and 95% CIs showing associations between saliva DNA methylation age derived from PedBE and DNAmTL methods and chronological age in children from the Lifeways birth cohort.