Whole Blood DNA Methylation Signatures of Diet Are Associated With Cardiovascular Disease Risk Factors and All-Cause Mortality

Jiantao Ma; Casey M. Rebholz; Kim V.E. Braun; Lindsay M. Reynolds; Stella Aslibekyan; Rui Xia; Niranjan G. Biligowda; Tianxiao Huan; Chunyu Liu; Michael M. Mendelson; Roby Joehanes; Emily A. Hu; Mara Z. Vitolins; Alexis C. Wood; Kurt Lohman; Carolina Ochoa-Rosales; Joyce Van Meurs; Andre Uitterlinden; Yongmei Liu; Mohamed A. Elhadad; Margit Heier; Melanie Waldenberger; Annette Peters; Elena Colicino; Eric A. Whitsel; Antoine Baldassari; Sina A. Gharib; Nona Sotoodehnia; Jennifer A. Brody; Colleen M. Sitlani; Toshiko Tanaka; W. David Hill; Janie Corley; Ian J. Deary; Yan Zhang; Ben Schöttker; Hermann Brenner; Maura E. Walker; Shumao Ye; Steve Nguyen; Jim Pankow; Ellen W. Demerath; Yinan Zheng; Lifang Hou; Liming Liang; Alice H. Lichtenstein; Frank B. Hu; Myriam Fornage; Trudy Voortman; Daniel Levy

doi:10.1161/CIRCGEN.119.002766

Whole Blood DNA Methylation Signatures of Diet Are Associated With Cardiovascular Disease Risk Factors and All-Cause Mortality

Jiantao Ma^*, Casey M. Rebholz, Kim V.E. Braun, Lindsay M. Reynolds, Stella Aslibekyan, Rui Xia, Niranjan G. Biligowda, Tianxiao Huan, Chunyu Liu, Michael M. Mendelson, Roby Joehanes, Emily A. Hu, Mara Z. Vitolins, Alexis C. Wood, Kurt Lohman, Carolina Ochoa-Rosales, Joyce Van Meurs, Andre Uitterlinden, Yongmei Liu, Mohamed A. ElhadadMargit Heier, Melanie Waldenberger, Annette Peters, Elena Colicino, Eric A. Whitsel, Antoine Baldassari, Sina A. Gharib, Nona Sotoodehnia, Jennifer A. Brody, Colleen M. Sitlani, Toshiko Tanaka, W. David Hill, Janie Corley, Ian J. Deary, Yan Zhang, Ben Schöttker, Hermann Brenner, Maura E. Walker, Shumao Ye, Steve Nguyen, Jim Pankow, Ellen W. Demerath, Yinan Zheng, Lifang Hou, Liming Liang, Alice H. Lichtenstein, Frank B. Hu, Myriam Fornage, Trudy Voortman, Daniel Levy

^*Corresponding author for this work

Preventive Medicine

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

44 Scopus citations

Abstract

Background: DNA methylation patterns associated with habitual diet have not been well studied. Methods: Diet quality was characterized using a Mediterranean-style diet score and the Alternative Healthy Eating Index score. We conducted ethnicity-specific and trans-ethnic epigenome-wide association analyses for diet quality and leukocyte-derived DNA methylation at over 400 000 CpGs (cytosine-guanine dinucleotides) in 5 population-based cohorts including 6662 European ancestry, 2702 African ancestry, and 360 Hispanic ancestry participants. For diet-associated CpGs identified in epigenome-wide analyses, we conducted Mendelian randomization (MR) analysis to examine their relations to cardiovascular disease risk factors and examined their longitudinal associations with all-cause mortality. Results: We identified 30 CpGs associated with either Mediterranean-style diet score or Alternative Healthy Eating Index, or both, in European ancestry participants. Among these CpGs, 12 CpGs were significantly associated with all-cause mortality (Bonferroni corrected P<1.6×10^-3). Hypermethylation of cg18181703 (SOCS3) was associated with higher scores of both Mediterranean-style diet score and Alternative Healthy Eating Index and lower risk for all-cause mortality (P=5.7×10^-15). Ten additional diet-associated CpGs were nominally associated with all-cause mortality (P<0.05). MR analysis revealed 8 putatively causal associations for 6 CpGs with 4 cardiovascular disease risk factors (body mass index, triglycerides, high-density lipoprotein cholesterol concentrations, and type 2 diabetes mellitus; Bonferroni corrected MR P<4.5×10^-4). For example, hypermethylation of cg11250194 (FADS2) was associated with lower triglyceride concentrations (MR, P=1.5×10^-14).and hypermethylation of cg02079413 (SNORA54; NAP1L4) was associated with body mass index (corrected MR, P=1×10^-6). Conclusions: Habitual diet quality was associated with differential peripheral leukocyte DNA methylation levels of 30 CpGs, most of which were also associated with multiple health outcomes, in European ancestry individuals. These findings demonstrate that integrative genomic analysis of dietary information may reveal molecular targets for disease prevention and treatment.

Original language	English (US)
Pages (from-to)	E002766
Journal	Circulation: Genomic and Precision Medicine
Volume	13
Issue number	4
DOIs	https://doi.org/10.1161/CIRCGEN.119.002766
State	Published - Aug 1 2020

Funding

Keywords

DNA methylation
cardiovascular disease
diet
epigenome
triglycerides

ASJC Scopus subject areas

Genetics
Cardiology and Cardiovascular Medicine
Genetics(clinical)

UN SDGs

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

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10.1161/CIRCGEN.119.002766

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Ma, J., Rebholz, C. M., Braun, K. V. E., Reynolds, L. M., Aslibekyan, S., Xia, R., Biligowda, N. G., Huan, T., Liu, C., Mendelson, M. M., Joehanes, R., Hu, E. A., Vitolins, M. Z., Wood, A. C., Lohman, K., Ochoa-Rosales, C., Van Meurs, J., Uitterlinden, A., Liu, Y., ... Levy, D. (2020). Whole Blood DNA Methylation Signatures of Diet Are Associated With Cardiovascular Disease Risk Factors and All-Cause Mortality. Circulation: Genomic and Precision Medicine, 13(4), E002766. https://doi.org/10.1161/CIRCGEN.119.002766

@article{79819703071240618d43ff59f5cae85b,

title = "Whole Blood DNA Methylation Signatures of Diet Are Associated With Cardiovascular Disease Risk Factors and All-Cause Mortality",

abstract = "Background: DNA methylation patterns associated with habitual diet have not been well studied. Methods: Diet quality was characterized using a Mediterranean-style diet score and the Alternative Healthy Eating Index score. We conducted ethnicity-specific and trans-ethnic epigenome-wide association analyses for diet quality and leukocyte-derived DNA methylation at over 400 000 CpGs (cytosine-guanine dinucleotides) in 5 population-based cohorts including 6662 European ancestry, 2702 African ancestry, and 360 Hispanic ancestry participants. For diet-associated CpGs identified in epigenome-wide analyses, we conducted Mendelian randomization (MR) analysis to examine their relations to cardiovascular disease risk factors and examined their longitudinal associations with all-cause mortality. Results: We identified 30 CpGs associated with either Mediterranean-style diet score or Alternative Healthy Eating Index, or both, in European ancestry participants. Among these CpGs, 12 CpGs were significantly associated with all-cause mortality (Bonferroni corrected P<1.6×10-3). Hypermethylation of cg18181703 (SOCS3) was associated with higher scores of both Mediterranean-style diet score and Alternative Healthy Eating Index and lower risk for all-cause mortality (P=5.7×10-15). Ten additional diet-associated CpGs were nominally associated with all-cause mortality (P<0.05). MR analysis revealed 8 putatively causal associations for 6 CpGs with 4 cardiovascular disease risk factors (body mass index, triglycerides, high-density lipoprotein cholesterol concentrations, and type 2 diabetes mellitus; Bonferroni corrected MR P<4.5×10-4). For example, hypermethylation of cg11250194 (FADS2) was associated with lower triglyceride concentrations (MR, P=1.5×10-14).and hypermethylation of cg02079413 (SNORA54; NAP1L4) was associated with body mass index (corrected MR, P=1×10-6). Conclusions: Habitual diet quality was associated with differential peripheral leukocyte DNA methylation levels of 30 CpGs, most of which were also associated with multiple health outcomes, in European ancestry individuals. These findings demonstrate that integrative genomic analysis of dietary information may reveal molecular targets for disease prevention and treatment.",

keywords = "DNA methylation, cardiovascular disease, diet, epigenome, triglycerides",

author = "Jiantao Ma and Rebholz, {Casey M.} and Braun, {Kim V.E.} and Reynolds, {Lindsay M.} and Stella Aslibekyan and Rui Xia and Biligowda, {Niranjan G.} and Tianxiao Huan and Chunyu Liu and Mendelson, {Michael M.} and Roby Joehanes and Hu, {Emily A.} and Vitolins, {Mara Z.} and Wood, {Alexis C.} and Kurt Lohman and Carolina Ochoa-Rosales and {Van Meurs}, Joyce and Andre Uitterlinden and Yongmei Liu and Elhadad, {Mohamed A.} and Margit Heier and Melanie Waldenberger and Annette Peters and Elena Colicino and Whitsel, {Eric A.} and Antoine Baldassari and Gharib, {Sina A.} and Nona Sotoodehnia and Brody, {Jennifer A.} and Sitlani, {Colleen M.} and Toshiko Tanaka and Hill, {W. David} and Janie Corley and Deary, {Ian J.} and Yan Zhang and Ben Sch{\"o}ttker and Hermann Brenner and Walker, {Maura E.} and Shumao Ye and Steve Nguyen and Jim Pankow and Demerath, {Ellen W.} and Yinan Zheng and Lifang Hou and Liming Liang and Lichtenstein, {Alice H.} and Hu, {Frank B.} and Myriam Fornage and Trudy Voortman and Daniel Levy",

year = "2020",

month = aug,

day = "1",

doi = "10.1161/CIRCGEN.119.002766",

language = "English (US)",

volume = "13",

pages = "E002766",

journal = "Circulation: Genomic and Precision Medicine",

issn = "2574-8300",

publisher = "Lippincott Williams and Wilkins Ltd.",

number = "4",

}

Ma, J, Rebholz, CM, Braun, KVE, Reynolds, LM, Aslibekyan, S, Xia, R, Biligowda, NG, Huan, T, Liu, C, Mendelson, MM, Joehanes, R, Hu, EA, Vitolins, MZ, Wood, AC, Lohman, K, Ochoa-Rosales, C, Van Meurs, J, Uitterlinden, A, Liu, Y, Elhadad, MA, Heier, M, Waldenberger, M, Peters, A, Colicino, E, Whitsel, EA, Baldassari, A, Gharib, SA, Sotoodehnia, N, Brody, JA, Sitlani, CM, Tanaka, T, Hill, WD, Corley, J, Deary, IJ, Zhang, Y, Schöttker, B, Brenner, H, Walker, ME, Ye, S, Nguyen, S, Pankow, J, Demerath, EW, Zheng, Y , Hou, L, Liang, L, Lichtenstein, AH, Hu, FB, Fornage, M, Voortman, T & Levy, D 2020, 'Whole Blood DNA Methylation Signatures of Diet Are Associated With Cardiovascular Disease Risk Factors and All-Cause Mortality', Circulation: Genomic and Precision Medicine, vol. 13, no. 4, pp. E002766. https://doi.org/10.1161/CIRCGEN.119.002766

TY - JOUR

T1 - Whole Blood DNA Methylation Signatures of Diet Are Associated With Cardiovascular Disease Risk Factors and All-Cause Mortality

AU - Ma, Jiantao

AU - Rebholz, Casey M.

AU - Braun, Kim V.E.

AU - Reynolds, Lindsay M.

AU - Aslibekyan, Stella

AU - Xia, Rui

AU - Biligowda, Niranjan G.

AU - Huan, Tianxiao

AU - Liu, Chunyu

AU - Mendelson, Michael M.

AU - Joehanes, Roby

AU - Hu, Emily A.

AU - Vitolins, Mara Z.

AU - Wood, Alexis C.

AU - Lohman, Kurt

AU - Ochoa-Rosales, Carolina

AU - Van Meurs, Joyce

AU - Uitterlinden, Andre

AU - Liu, Yongmei

AU - Elhadad, Mohamed A.

AU - Heier, Margit

AU - Waldenberger, Melanie

AU - Peters, Annette

AU - Colicino, Elena

AU - Whitsel, Eric A.

AU - Baldassari, Antoine

AU - Gharib, Sina A.

AU - Sotoodehnia, Nona

AU - Brody, Jennifer A.

AU - Sitlani, Colleen M.

AU - Tanaka, Toshiko

AU - Hill, W. David

AU - Corley, Janie

AU - Deary, Ian J.

AU - Zhang, Yan

AU - Schöttker, Ben

AU - Brenner, Hermann

AU - Walker, Maura E.

AU - Ye, Shumao

AU - Nguyen, Steve

AU - Pankow, Jim

AU - Demerath, Ellen W.

AU - Zheng, Yinan

AU - Hou, Lifang

AU - Liang, Liming

AU - Lichtenstein, Alice H.

AU - Hu, Frank B.

AU - Fornage, Myriam

AU - Voortman, Trudy

AU - Levy, Daniel

PY - 2020/8/1

Y1 - 2020/8/1

N2 - Background: DNA methylation patterns associated with habitual diet have not been well studied. Methods: Diet quality was characterized using a Mediterranean-style diet score and the Alternative Healthy Eating Index score. We conducted ethnicity-specific and trans-ethnic epigenome-wide association analyses for diet quality and leukocyte-derived DNA methylation at over 400 000 CpGs (cytosine-guanine dinucleotides) in 5 population-based cohorts including 6662 European ancestry, 2702 African ancestry, and 360 Hispanic ancestry participants. For diet-associated CpGs identified in epigenome-wide analyses, we conducted Mendelian randomization (MR) analysis to examine their relations to cardiovascular disease risk factors and examined their longitudinal associations with all-cause mortality. Results: We identified 30 CpGs associated with either Mediterranean-style diet score or Alternative Healthy Eating Index, or both, in European ancestry participants. Among these CpGs, 12 CpGs were significantly associated with all-cause mortality (Bonferroni corrected P<1.6×10-3). Hypermethylation of cg18181703 (SOCS3) was associated with higher scores of both Mediterranean-style diet score and Alternative Healthy Eating Index and lower risk for all-cause mortality (P=5.7×10-15). Ten additional diet-associated CpGs were nominally associated with all-cause mortality (P<0.05). MR analysis revealed 8 putatively causal associations for 6 CpGs with 4 cardiovascular disease risk factors (body mass index, triglycerides, high-density lipoprotein cholesterol concentrations, and type 2 diabetes mellitus; Bonferroni corrected MR P<4.5×10-4). For example, hypermethylation of cg11250194 (FADS2) was associated with lower triglyceride concentrations (MR, P=1.5×10-14).and hypermethylation of cg02079413 (SNORA54; NAP1L4) was associated with body mass index (corrected MR, P=1×10-6). Conclusions: Habitual diet quality was associated with differential peripheral leukocyte DNA methylation levels of 30 CpGs, most of which were also associated with multiple health outcomes, in European ancestry individuals. These findings demonstrate that integrative genomic analysis of dietary information may reveal molecular targets for disease prevention and treatment.

AB - Background: DNA methylation patterns associated with habitual diet have not been well studied. Methods: Diet quality was characterized using a Mediterranean-style diet score and the Alternative Healthy Eating Index score. We conducted ethnicity-specific and trans-ethnic epigenome-wide association analyses for diet quality and leukocyte-derived DNA methylation at over 400 000 CpGs (cytosine-guanine dinucleotides) in 5 population-based cohorts including 6662 European ancestry, 2702 African ancestry, and 360 Hispanic ancestry participants. For diet-associated CpGs identified in epigenome-wide analyses, we conducted Mendelian randomization (MR) analysis to examine their relations to cardiovascular disease risk factors and examined their longitudinal associations with all-cause mortality. Results: We identified 30 CpGs associated with either Mediterranean-style diet score or Alternative Healthy Eating Index, or both, in European ancestry participants. Among these CpGs, 12 CpGs were significantly associated with all-cause mortality (Bonferroni corrected P<1.6×10-3). Hypermethylation of cg18181703 (SOCS3) was associated with higher scores of both Mediterranean-style diet score and Alternative Healthy Eating Index and lower risk for all-cause mortality (P=5.7×10-15). Ten additional diet-associated CpGs were nominally associated with all-cause mortality (P<0.05). MR analysis revealed 8 putatively causal associations for 6 CpGs with 4 cardiovascular disease risk factors (body mass index, triglycerides, high-density lipoprotein cholesterol concentrations, and type 2 diabetes mellitus; Bonferroni corrected MR P<4.5×10-4). For example, hypermethylation of cg11250194 (FADS2) was associated with lower triglyceride concentrations (MR, P=1.5×10-14).and hypermethylation of cg02079413 (SNORA54; NAP1L4) was associated with body mass index (corrected MR, P=1×10-6). Conclusions: Habitual diet quality was associated with differential peripheral leukocyte DNA methylation levels of 30 CpGs, most of which were also associated with multiple health outcomes, in European ancestry individuals. These findings demonstrate that integrative genomic analysis of dietary information may reveal molecular targets for disease prevention and treatment.

KW - DNA methylation

KW - cardiovascular disease

KW - diet

KW - epigenome

KW - triglycerides

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UR - http://www.scopus.com/inward/citedby.url?scp=85089768397&partnerID=8YFLogxK

U2 - 10.1161/CIRCGEN.119.002766

DO - 10.1161/CIRCGEN.119.002766

M3 - Article

C2 - 32525743

AN - SCOPUS:85089768397

SN - 2574-8300

VL - 13

SP - E002766

JO - Circulation: Genomic and Precision Medicine

JF - Circulation: Genomic and Precision Medicine

IS - 4

ER -

Whole Blood DNA Methylation Signatures of Diet Are Associated With Cardiovascular Disease Risk Factors and All-Cause Mortality

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UN SDGs

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