Epigenome-wide association study of diet quality in the Women’s Health Initiative and TwinsUK cohort

Whitney L. Do; Eric A. Whitsel; Ricardo Costeira; Olatz M. Masachs; Caroline I. Le Roy; Jordana T. Bell; Lisa R. Staimez; Aryeh D. Stein; Alicia K. Smith; Steve Horvath; Themistocles L. Assimes; Simin Liu; Jo Ann E. Manson; Aladdin H. Shadyab; Yun Li; Lifang Hou; Parveen Bhatti; Kristina Jordahl; K. M. Venkat Narayan; Karen N. Conneely

doi:10.1093/ije/dyaa215

Epigenome-wide association study of diet quality in the Women’s Health Initiative and TwinsUK cohort

Whitney L. Do^*, Eric A. Whitsel, Ricardo Costeira, Olatz M. Masachs, Caroline I. Le Roy, Jordana T. Bell, Lisa R. Staimez, Aryeh D. Stein, Alicia K. Smith, Steve Horvath, Themistocles L. Assimes, Simin Liu, Jo Ann E. Manson, Aladdin H. Shadyab, Yun Li, Lifang Hou, Parveen Bhatti, Kristina Jordahl, K. M. Venkat Narayan, Karen N. Conneely

^*Corresponding author for this work

Preventive Medicine

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

21 Scopus citations

Abstract

Background: Diet quality is a risk factor for chronic disease and mortality. Differential DNA methylation across the epigenome has been associated with chronic disease risk. Whether diet quality is associated with differential methylation is unknown. This study assessed whether diet quality was associated with differential DNA methylation measured across 445 548 loci in the Women’s Health Initiative (WHI) and the TwinsUK cohort. Design: The discovery cohort consisted of 4355 women from the WHI. The replication cohort consisted of 571 mono- and dizygotic twins from the TwinsUK cohort. DNA methylation was measured in whole blood using the Illumina Infinium HumanMethylation450 Beadchip. Diet quality was assessed using the Alternative Healthy Eating Index 2010 (AHEI-2010). A meta-analysis, stratified by study cohort, was performed using generalized linear models that regressed methylation on AHEI-2010, adjusting for cell composition, chip number and location, study characteristics, principal components of genetic relatedness, age, smoking status, race/ethnicity and body mass index (BMI). Statistical significance was defined as a false discovery rate < 0.05. Significant sites were tested for replication in the TwinsUK cohort, with significant replication defined by P < 0.05 and a consistent direction. Results: Diet quality was significantly associated with differential DNA methylation at 428 cytosine-phosphate-guanine (CpG) sites in the discovery cohort. A total of 24 CpG sites were consistent with replication in the TwinsUK cohort, more than would be expected by chance (P ¼ 2.7x10^-4), with one site replicated in both the blood and adipose tissue (cg16379999 located in the body of SEL1L). Conclusions: Diet quality was associated with methylation at 24 CpG sites, several of which have been associated with adiposity, inflammation and dysglycaemia. These findings may provide insight into pathways through which diet influences chronic disease.

Original language	English (US)
Pages (from-to)	675-684
Number of pages	10
Journal	International journal of epidemiology
Volume	50
Issue number	2
DOIs	https://doi.org/10.1093/ije/dyaa215
State	Published - Apr 1 2021

Funding

The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. The TwinsUK study was funded by the Wellcome Trust; European Community\u2019s Seventh Framework Programme (FP7/2007\u20132013); National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy\u2019s and St Thomas\u2019 NHS Foundation Trust in partnership with King\u2019s College London. The TwinsUK methylation study received support from the ESRC (ES/N000404/1 to J.T.B.) and the Joint Programming Initiative HDHL DIMENSION (administered by the BBSRC UK, BB/ S020845/1 to J.T.B.). K.M.V.N., L.S. and W.L.D. were supported in part by the National Institute of Diabetes And Digestive And Kidney Diseases of the National Institutes of Health under award number P30DK111024 and the Hubert Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. W.L.D. was supported in part by the Nalini and Ravi Saligram Scholarship. This work was supported in part by National Institute of Environmental Health Sciences grant R01-ES020836 (L.H., E.A.W.) and National Heart, Lung, and Blood Institute contract HHSN268201100046C (K.N.C.). P.B. and K.J. were supported by the American Cancer Society (125299-RSG-13\u2013100-01-CCE) with additional support for K.J. through National Cancer Institute training grants (R25 CA094880 and T32 CA094880). S.H. acknowledges support by U01 AG060908/AG/NIA NIH HHS/US. Y.L. was supported through R01 HL129132.

Keywords

EWAS
Epigenome
Women’s Health Initiative
diet quality
dietary epigenetics

ASJC Scopus subject areas

Epidemiology

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10.1093/ije/dyaa215

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Do, W. L., Whitsel, E. A., Costeira, R., Masachs, O. M., Le Roy, C. I., Bell, J. T., Staimez, L. R., Stein, A. D., Smith, A. K., Horvath, S., Assimes, T. L., Liu, S., Manson, J. A. E., Shadyab, A. H., Li, Y., Hou, L., Bhatti, P., Jordahl, K., Venkat Narayan, K. M., & Conneely, K. N. (2021). Epigenome-wide association study of diet quality in the Women’s Health Initiative and TwinsUK cohort. International journal of epidemiology, 50(2), 675-684. https://doi.org/10.1093/ije/dyaa215

@article{a7287a64b3774d81b83c03ec4350977d,

title = "Epigenome-wide association study of diet quality in the Women{\textquoteright}s Health Initiative and TwinsUK cohort",

abstract = "Background: Diet quality is a risk factor for chronic disease and mortality. Differential DNA methylation across the epigenome has been associated with chronic disease risk. Whether diet quality is associated with differential methylation is unknown. This study assessed whether diet quality was associated with differential DNA methylation measured across 445 548 loci in the Women{\textquoteright}s Health Initiative (WHI) and the TwinsUK cohort. Design: The discovery cohort consisted of 4355 women from the WHI. The replication cohort consisted of 571 mono- and dizygotic twins from the TwinsUK cohort. DNA methylation was measured in whole blood using the Illumina Infinium HumanMethylation450 Beadchip. Diet quality was assessed using the Alternative Healthy Eating Index 2010 (AHEI-2010). A meta-analysis, stratified by study cohort, was performed using generalized linear models that regressed methylation on AHEI-2010, adjusting for cell composition, chip number and location, study characteristics, principal components of genetic relatedness, age, smoking status, race/ethnicity and body mass index (BMI). Statistical significance was defined as a false discovery rate < 0.05. Significant sites were tested for replication in the TwinsUK cohort, with significant replication defined by P < 0.05 and a consistent direction. Results: Diet quality was significantly associated with differential DNA methylation at 428 cytosine-phosphate-guanine (CpG) sites in the discovery cohort. A total of 24 CpG sites were consistent with replication in the TwinsUK cohort, more than would be expected by chance (P ¼ 2.7x10-4), with one site replicated in both the blood and adipose tissue (cg16379999 located in the body of SEL1L). Conclusions: Diet quality was associated with methylation at 24 CpG sites, several of which have been associated with adiposity, inflammation and dysglycaemia. These findings may provide insight into pathways through which diet influences chronic disease.",

keywords = "EWAS, Epigenome, Women{\textquoteright}s Health Initiative, diet quality, dietary epigenetics",

author = "Do, {Whitney L.} and Whitsel, {Eric A.} and Ricardo Costeira and Masachs, {Olatz M.} and {Le Roy}, {Caroline I.} and Bell, {Jordana T.} and Staimez, {Lisa R.} and Stein, {Aryeh D.} and Smith, {Alicia K.} and Steve Horvath and Assimes, {Themistocles L.} and Simin Liu and Manson, {Jo Ann E.} and Shadyab, {Aladdin H.} and Yun Li and Lifang Hou and Parveen Bhatti and Kristina Jordahl and {Venkat Narayan}, {K. M.} and Conneely, {Karen N.}",

year = "2021",

month = apr,

day = "1",

doi = "10.1093/ije/dyaa215",

language = "English (US)",

volume = "50",

pages = "675--684",

journal = "International journal of epidemiology",

issn = "0300-5771",

publisher = "Oxford University Press",

number = "2",

}

Do, WL, Whitsel, EA, Costeira, R, Masachs, OM, Le Roy, CI, Bell, JT, Staimez, LR, Stein, AD, Smith, AK, Horvath, S, Assimes, TL, Liu, S, Manson, JAE, Shadyab, AH, Li, Y, Hou, L, Bhatti, P, Jordahl, K, Venkat Narayan, KM & Conneely, KN 2021, 'Epigenome-wide association study of diet quality in the Women’s Health Initiative and TwinsUK cohort', International journal of epidemiology, vol. 50, no. 2, pp. 675-684. https://doi.org/10.1093/ije/dyaa215

TY - JOUR

T1 - Epigenome-wide association study of diet quality in the Women’s Health Initiative and TwinsUK cohort

AU - Do, Whitney L.

AU - Whitsel, Eric A.

AU - Costeira, Ricardo

AU - Masachs, Olatz M.

AU - Le Roy, Caroline I.

AU - Bell, Jordana T.

AU - Staimez, Lisa R.

AU - Stein, Aryeh D.

AU - Smith, Alicia K.

AU - Horvath, Steve

AU - Assimes, Themistocles L.

AU - Liu, Simin

AU - Manson, Jo Ann E.

AU - Shadyab, Aladdin H.

AU - Li, Yun

AU - Hou, Lifang

AU - Bhatti, Parveen

AU - Jordahl, Kristina

AU - Venkat Narayan, K. M.

AU - Conneely, Karen N.

PY - 2021/4/1

Y1 - 2021/4/1

N2 - Background: Diet quality is a risk factor for chronic disease and mortality. Differential DNA methylation across the epigenome has been associated with chronic disease risk. Whether diet quality is associated with differential methylation is unknown. This study assessed whether diet quality was associated with differential DNA methylation measured across 445 548 loci in the Women’s Health Initiative (WHI) and the TwinsUK cohort. Design: The discovery cohort consisted of 4355 women from the WHI. The replication cohort consisted of 571 mono- and dizygotic twins from the TwinsUK cohort. DNA methylation was measured in whole blood using the Illumina Infinium HumanMethylation450 Beadchip. Diet quality was assessed using the Alternative Healthy Eating Index 2010 (AHEI-2010). A meta-analysis, stratified by study cohort, was performed using generalized linear models that regressed methylation on AHEI-2010, adjusting for cell composition, chip number and location, study characteristics, principal components of genetic relatedness, age, smoking status, race/ethnicity and body mass index (BMI). Statistical significance was defined as a false discovery rate < 0.05. Significant sites were tested for replication in the TwinsUK cohort, with significant replication defined by P < 0.05 and a consistent direction. Results: Diet quality was significantly associated with differential DNA methylation at 428 cytosine-phosphate-guanine (CpG) sites in the discovery cohort. A total of 24 CpG sites were consistent with replication in the TwinsUK cohort, more than would be expected by chance (P ¼ 2.7x10-4), with one site replicated in both the blood and adipose tissue (cg16379999 located in the body of SEL1L). Conclusions: Diet quality was associated with methylation at 24 CpG sites, several of which have been associated with adiposity, inflammation and dysglycaemia. These findings may provide insight into pathways through which diet influences chronic disease.

AB - Background: Diet quality is a risk factor for chronic disease and mortality. Differential DNA methylation across the epigenome has been associated with chronic disease risk. Whether diet quality is associated with differential methylation is unknown. This study assessed whether diet quality was associated with differential DNA methylation measured across 445 548 loci in the Women’s Health Initiative (WHI) and the TwinsUK cohort. Design: The discovery cohort consisted of 4355 women from the WHI. The replication cohort consisted of 571 mono- and dizygotic twins from the TwinsUK cohort. DNA methylation was measured in whole blood using the Illumina Infinium HumanMethylation450 Beadchip. Diet quality was assessed using the Alternative Healthy Eating Index 2010 (AHEI-2010). A meta-analysis, stratified by study cohort, was performed using generalized linear models that regressed methylation on AHEI-2010, adjusting for cell composition, chip number and location, study characteristics, principal components of genetic relatedness, age, smoking status, race/ethnicity and body mass index (BMI). Statistical significance was defined as a false discovery rate < 0.05. Significant sites were tested for replication in the TwinsUK cohort, with significant replication defined by P < 0.05 and a consistent direction. Results: Diet quality was significantly associated with differential DNA methylation at 428 cytosine-phosphate-guanine (CpG) sites in the discovery cohort. A total of 24 CpG sites were consistent with replication in the TwinsUK cohort, more than would be expected by chance (P ¼ 2.7x10-4), with one site replicated in both the blood and adipose tissue (cg16379999 located in the body of SEL1L). Conclusions: Diet quality was associated with methylation at 24 CpG sites, several of which have been associated with adiposity, inflammation and dysglycaemia. These findings may provide insight into pathways through which diet influences chronic disease.

KW - EWAS

KW - Epigenome

KW - Women’s Health Initiative

KW - diet quality

KW - dietary epigenetics

UR - http://www.scopus.com/inward/record.url?scp=85107082220&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85107082220&partnerID=8YFLogxK

U2 - 10.1093/ije/dyaa215

DO - 10.1093/ije/dyaa215

M3 - Article

C2 - 33354722

AN - SCOPUS:85107082220

SN - 0300-5771

VL - 50

SP - 675

EP - 684

JO - International journal of epidemiology

JF - International journal of epidemiology

IS - 2

ER -

Epigenome-wide association study of diet quality in the Women’s Health Initiative and TwinsUK cohort

Abstract

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