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. Wang; Phillip 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

doi:10.1080/15592294.2023.2211361

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^*

^*Corresponding author for this work

Department of Biomedical Sciences (Master's Program in Clinical Trials Assessment)

Research output: Contribution to journal › Journal Article › peer-review

3 Scopus citations

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 language	English
Article number	2211361
Pages (from-to)	2211361
Journal	Epigenetics
Volume	18
Issue number	1
DOIs	https://doi.org/10.1080/15592294.2023.2211361
State	Published - 12 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.

Keywords

Epigenetics
Vitamin C
Vitamin E
diet
epidemiology
Humans
Epigenesis, Genetic
Vitamins/pharmacology
DNA Methylation
Ascorbic Acid
Genome-Wide Association Study/methods
CpG Islands
Epigenome

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1080/15592294.2023.2211361

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Keshawarz, A., Joehanes, R., Ma, J., Lee, G. Y., Costeira, R., Tsai, P. C., Masachs, O. M., Bell, J. T., Wilson, R., Thorand, B., Winkelmann, J., Peters, A., Linseisen, J., Waldenberger, M., Lehtimäki, T., Mishra, P. P., Kähönen, M., Raitakari, O., Helminen, M., ... Levy, D. (2023). Dietary and supplemental intake of vitamins C and E is associated with altered DNA methylation in an epigenome-wide association study meta-analysis. Epigenetics, 18(1), 2211361. Article 2211361. https://doi.org/10.1080/15592294.2023.2211361

@article{ee656a5f769b4a52b40de6f89f2e84e8,

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

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.",

keywords = "Epigenetics, Vitamin C, Vitamin E, diet, epidemiology, Humans, Epigenesis, Genetic, Vitamins/pharmacology, DNA Methylation, Ascorbic Acid, Genome-Wide Association Study/methods, CpG Islands, Epigenome",

author = "Amena Keshawarz and Roby Joehanes and Jiantao Ma and Lee, {Gha Young} and Ricardo Costeira and Tsai, {Pei Chien} and Masachs, {Olatz M.} and Bell, {Jordana T.} and Rory Wilson and Barbara Thorand and Juliane Winkelmann and Annette Peters and Jakob Linseisen and Melanie Waldenberger and Terho Lehtim{\"a}ki and Mishra, {Pashupati P.} and Mika K{\"a}h{\"o}nen and Olli Raitakari and Mika Helminen and Wang, {Carol A.} and Melton, {Phillip E.} and Huang, {Rae Chi} and Pennell, {Craig E.} and O{\textquoteright}Sullivan, {Therese A.} and Carolina Ochoa-Rosales and Trudy Voortman and {van Meurs}, {Joyce B.J.} and Young, {Kristin L.} and Misa Graff and Yujie Wang and Kiel, {Douglas P.} and Smith, {Caren E.} and Jacques, {Paul F.} and Daniel Levy",

note = "Publisher Copyright: {\textcopyright} This work was authored as part of the Contributor{\textquoteright}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.",

year = "2023",

month = dec,

doi = "10.1080/15592294.2023.2211361",

language = "英语",

volume = "18",

pages = "2211361",

journal = "Epigenetics",

issn = "1559-2294",

publisher = "Taylor and Francis Ltd.",

number = "1",

}

Keshawarz, A, Joehanes, R, Ma, J, Lee, GY, Costeira, R, Tsai, PC, Masachs, OM, Bell, JT, Wilson, R, Thorand, B, Winkelmann, J, Peters, A, Linseisen, J, Waldenberger, M, Lehtimäki, T, Mishra, PP, Kähönen, M, Raitakari, O, Helminen, M, Wang, CA, Melton, PE, Huang, RC, Pennell, CE, O’Sullivan, TA, Ochoa-Rosales, C, Voortman, T, van Meurs, JBJ, Young, KL, Graff, M, Wang, Y, Kiel, DP, Smith, CE, Jacques, PF & Levy, D 2023, 'Dietary and supplemental intake of vitamins C and E is associated with altered DNA methylation in an epigenome-wide association study meta-analysis', Epigenetics, vol. 18, no. 1, 2211361, pp. 2211361. https://doi.org/10.1080/15592294.2023.2211361

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 - 2023/12

Y1 - 2023/12

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

KW - Humans

KW - Epigenesis, Genetic

KW - Vitamins/pharmacology

KW - DNA Methylation

KW - Ascorbic Acid

KW - Genome-Wide Association Study/methods

KW - CpG Islands

KW - Epigenome

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 - 文章

C2 - 37233989

AN - SCOPUS:85160458405

SN - 1559-2294

VL - 18

SP - 2211361

JO - Epigenetics

JF - Epigenetics

IS - 1

M1 - 2211361

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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