Dietary and supplemental intake of vitamins C and E is associated with altered DNA methylation in an epigenome-wide association study meta-analysis

Amena Keshawarz, Roby Joehanes, Jiantao Ma, Gha Young Lee, Ricardo Costeira, Pei Chien Tsai, Olatz M. Masachs, Jordana T. Bell, Rory Wilson, Barbara Thorand, Juliane Winkelmann, Annette Peters, Jakob Linseisen, Melanie Waldenberger, Terho Lehtimäki, Pashupati P. Mishra, Mika Kähönen, Olli Raitakari, Mika Helminen, Carol A. WangPhillip E. Melton, Rae Chi Huang, Craig E. Pennell, Therese A. O'Sullivan, Carolina Ochoa-Rosales, Trudy Voortman, Joyce B.J. van Meurs, Kristin L. Young, Misa Graff, Yujie Wang, Douglas P. Kiel, Caren E. Smith, Paul F. Jacques, Daniel Levy

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Abstract

BACKGROUND: Dietary intake of antioxidants such as vitamins C and E protect against oxidative stress, and may also be associated with altered DNA methylation patterns. METHODS: We meta-analysed epigenome-wide association study (EWAS) results from 11,866 participants across eight population-based cohorts to evaluate the association between self-reported dietary and supplemental intake of vitamins C and E with DNA methylation. EWAS were adjusted for age, sex, BMI, caloric intake, blood cell type proportion, smoking status, alcohol consumption, and technical covariates. Significant results of the meta-analysis were subsequently evaluated in gene set enrichment analysis (GSEA) and expression quantitative trait methylation (eQTM) analysis. RESULTS: In meta-analysis, methylation at 4,656 CpG sites was significantly associated with vitamin C intake at FDR ≤ 0.05. The most significant CpG sites associated with vitamin C (at FDR ≤ 0.01) were enriched for pathways associated with systems development and cell signalling in GSEA, and were associated with downstream expression of genes enriched in the immune response in eQTM analysis. Furthermore, methylation at 160 CpG sites was significantly associated with vitamin E intake at FDR ≤ 0.05, but GSEA and eQTM analysis of the top most significant CpG sites associated with vitamin E did not identify significant enrichment of any biological pathways investigated. CONCLUSIONS: We identified significant associations of many CpG sites with vitamin C and E intake, and our results suggest that vitamin C intake may be associated with systems development and the immune response.

Original languageEnglish
Article number2211361
Number of pages15
JournalEpigenetics
Volume18
Issue number1
Early online date26 May 2023
DOIs
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
© This work was authored as part of the Contributor’s official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 USC 105, no copyright protection is available for such works under US Law.

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