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

被引：53

作者：

Ma, Jiantao ^{[1
,2
,3
,4
]}

Rebholz, Casey M. ^{[5
]}

Braun, Kim V. E. ^{[6
]}

Reynolds, Lindsay M. ^{[8
]}

Aslibekyan, Stella ^{[10
]}

Xia, Rui ^{[11
]}

Biligowda, Niranjan G. ^{[10
]}

Huan, Tianxiao ^{[3
,4
]}

Liu, Chunyu ^{[3
,4
,12
]}

Mendelson, Michael M. ^{[3
,4
,13
]}

Joehanes, Roby ^{[3
,4
]}

Hu, Emily A. ^{[5
]}

Vitolins, Mara Z. ^{[8
]}

Wood, Alexis C. ^{[14
]}

Lohman, Kurt ^{[9
]}

Ochoa-Rosales, Carolina ^{[6
,15
]}

van Meurs, Joyce ^{[7
]}

Uitterlinden, Andre ^{[7
]}

Liu, Yongmei ^{[8
]}

Elhadad, Mohamed A. ^{[16
,17
,18
]}

Heier, Margit ^{[16
,19
]}

Waldenberger, Melanie ^{[16
,17
,18
]}

Peters, Annette ^{[16
,17
,18
]}

Colicino, Elena ^{[20
]}

Whitsel, Eric A. ^{[21
,22
]}

Baldassari, Antoine ^{[21
]}

Gharib, Sina A. ^{[23
]}

Sotoodehnia, Nona ^{[23
]}

Brody, Jennifer A. ^{[23
]}

Sitlani, Colleen M. ^{[23
]}

Tanaka, Toshiko ^{[24
]}

Hill, W. David ^{[25
,26
]}

Corley, Janie ^{[25
,26
]}

Deary, Ian J. ^{[25
,26
]}

Zhang, Yan ^{[27
]}

Schoettker, Ben ^{[27
,28
]}

Brenner, Hermann ^{[27
,28
]}

Walker, Maura E. ^{[29
]}

Ye, Shumao ^{[2
]}

Nguyen, Steve ^{[30
]}

Pankow, Jim ^{[30
]}

Demerath, Ellen W. ^{[30
]}

Zheng, Yinan ^{[31
,32
]}

Hou, Lifang ^{[31
,32
]}

Liang, Liming ^{[33
,34
]}

Lichtenstein, Alice H. ^{[2
]}

Hu, Frank B. ^{[33
,35
]}

Fornage, Myriam ^{[11
]}

Voortman, Trudy ^{[6
]}

Levy, Daniel ^{[3
,4
]}

机构：

[1] Tufts Univ, USDA, Friedman Sch Nutr Sci & Policy, Nutr Epidemiol & Data Sci,Human Nutr Res Ctr Agin, Boston, MA 02111 USA

[2] Tufts Univ, USDA, Cardiovasc Nutr Lab, Human Nutr Res Ctr Aging, Boston, MA 02111 USA

[3] NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA

[4] Framingham Heart Dis Epidemiol Study, Framingham, MA USA

[5] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA

[6] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[7] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands

[8] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC 27101 USA

[9] Wake Forest Sch Med, Dept Biostat, Winston Salem, NC 27101 USA

[10] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA

[11] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA

[12] Boston Univ, Dept Biostat, Boston, MA 02215 USA

[13] Harvard Med Sch, Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA

[14] USDA ARS, Childrens Nutr Rsrch Ctr, Baylor Coll Med, Houston, TX USA

[15] Univ Concepcion, Ctr Vida Saludable, Concepcion, Bio Bio, Chile

[16] German Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany

[17] German Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany

[18] Univ Hosp Augsburg, DZHK German Ctr Cardiovasc Rsrch, Partner Site Munich Heart Alliance, Augsburg, Germany

[19] Univ Hosp Augsburg, KORA Study Ctr, Augsburg, Germany

[20] Columbia Univ, Dept Environm Hlth Sci, New York, NY USA

[21] Univ N Carolina, Sch Med, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27515 USA

[22] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC 27515 USA

[23] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[24] NIA, Longitudinal Study Sect, NIH, Bethesda, MD 20892 USA

[25] Univ Edinburgh, Birth Cohorts, Edinburgh, Midlothian, Scotland

[26] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland

[27] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany

[28] Heidelberg Univ, Network Aging Res NAR, Heidelberg, Germany

[29] Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, Boston, MA 02118 USA

[30] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA

[31] Northwestern Univ, Feinberg Sch Med, Ctr Populat Epigenet, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA

[32] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA

[33] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[34] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA

[35] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA

来源：

CIRCULATION-GENOMIC AND PRECISION MEDICINE | 2020年 / 13卷 / 04期

基金：

美国国家卫生研究院;

关键词：

cardiovascular disease; diet; DNA methylation; epigenome; triglycerides; EPIGENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; MEDITERRANEAN DIET; PERIPHERAL-BLOOD; ADHERENCE; QUALITY; INDEX; ACIDS;

D O I：

10.1161/CIRCGEN.119.002766

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 correctedP<1.6x10(-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=5.7x10(-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 MRP<4.5x10(-4)). For example, hypermethylation of cg11250194 (FADS2) was associated with lower triglyceride concentrations (MR,P=1.5x10(-14)).and hypermethylation of cg02079413 (SNORA54;NAP1L4) was associated with body mass index (corrected MR,P=1x10(-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.

引用

页数：10

共 36 条

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