TY - JOUR
T1 - Dietary and supplemental intake of vitamins C and E is associated with altered DNA methylation in an epigenome-wide association study meta-analysis
AU - Keshawarz, Amena
AU - Joehanes, Roby
AU - Ma, Jiantao
AU - Lee, Gha Young
AU - Costeira, Ricardo
AU - Tsai, Pei Chien
AU - Masachs, Olatz M.
AU - Bell, Jordana T.
AU - Wilson, Rory
AU - Thorand, Barbara
AU - Winkelmann, Juliane
AU - Peters, Annette
AU - Linseisen, Jakob
AU - Waldenberger, Melanie
AU - Lehtimäki, Terho
AU - Mishra, Pashupati P.
AU - Kähönen, Mika
AU - Raitakari, Olli
AU - Helminen, Mika
AU - Wang, Carol A.
AU - Melton, Phillip E.
AU - Huang, Rae Chi
AU - Pennell, Craig E.
AU - O’Sullivan, Therese A.
AU - Ochoa-Rosales, Carolina
AU - Voortman, Trudy
AU - van Meurs, Joyce B.J.
AU - Young, Kristin L.
AU - Graff, Misa
AU - Wang, Yujie
AU - Kiel, Douglas P.
AU - Smith, Caren E.
AU - Jacques, Paul F.
AU - Levy, Daniel
N1 - 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.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Epigenetics
KW - Vitamin C
KW - Vitamin E
KW - diet
KW - epidemiology
UR - http://www.scopus.com/inward/record.url?scp=85160458405&partnerID=8YFLogxK
U2 - 10.1080/15592294.2023.2211361
DO - 10.1080/15592294.2023.2211361
M3 - Article
C2 - 37233989
AN - SCOPUS:85160458405
SN - 1559-2294
VL - 18
JO - Epigenetics
JF - Epigenetics
IS - 1
M1 - 2211361
ER -
