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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.* ; Elhadad, M.A. ; Heier, M.* ; Waldenberger, M. ; Peters, A. ; Colicino, E.* ; Whitsel, E.A.* ; Baldassari, A.* ; Gharib, S.A.* ; Sotoodehnia, N.* ; Brody, J.A.* ; Sitlani, C.M.* ; Tanaka, T.* ; Hill, W.D.* ; Corley, J.* ; Deary, I.J.* ; Zhang, Y.* ; Schöttker, B.* ; Brenner, H.* ; Walker, M.E.* ; Ye, S.* ; Nguyen, S.* ; Pankow, J.* ; Demerath, E.W.* ; Zheng, Y.* ; Hou, L.* ; Liang, L.* ; Lichtenstein, A.H.* ; Hu, F.B.* ; Fornage, M.* ; Voortman, T.* ; Levy, D.*

Whole blood DNA methylation signatures of diet are associated with cardiovascular disease risk factors and all-cause mortality.

Circ. Genom. Precis. Med. 13:e002766 (2020)
Postprint DOI Verlagsversion bestellen
Open Access Green
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cardiovascular Disease ; Diet ; Dna Methylation ; Epigenome ; Triglycerides; Epigenome-wide Association; Coronary-heart-disease; Mediterranean Diet; Peripheral-blood; Adherence; Quality; Index; Acids
ISSN (print) / ISBN 2574-8300
e-ISSN 2574-8300
Quellenangaben Band: 13, Heft: 4, Seiten: , Artikelnummer: e002766 Supplement: ,
Verlag Lippincott Williams & Wilkins
Verlagsort Philadelphia, Pa.
Begutachtungsstatus Peer reviewed
Förderungen NIA
Federal Ministry of Family Affairs, Senior Citizens, Women and Youth (Berlin, Germany)
Federal Ministry of Education and Research (Berlin, Germany)
Baden-Wurttemberg state Ministry of Science, Research and Arts (Stuttgart, Germany)
Saarland state Ministry for Social Affairs, Health, Women and Family Affairs (Saarbrucken, Germany)
NIH NHLBI
Mentored Research Scientist Development Award from the National Institute of Diabetes and Digestive and Kidney Diseases
National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services
Center for Information Technology, NIH, Bethesda, MD
Division of Intramural Research, National Heart, Lung, and Blood Institute
Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD
National Institutes of Health
National Institute of Environmental Health Sciences
Intramural Research Program of the National Institutes of Health (NIH): National Heart Lung and Blood Institute, National Institute on Aging
NIH T32
Genetic Laboratory of the Department of Internal Medicine, Erasmus MC
Netherlands Organization for Scientific research (NWO)
MESA
National Heart, Lung, and Blood Institute (NHLBI)
National Heart, Lung, and Blood Institute
CONICYT PAI/INDUSTRIA
State of Bavaria
Helmholtz Zentrum Munchen-German Research Center for Environmental Health - German Federal Ministry of Education and Research (BMBF)
National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC)
National Center for Advancing Translational Sciences
Locke Charitable Foundation
Alpha Phi Foundation
Laughlin Family
Munich Center of Health Sciences (MC-Health)
Ludwig-Maximilians Universitat
LM Uinnovativ
National Institute of Environmental Health Science
National Heart, Lung and Blood Institute, US Department of Health and Human Services
German Federal Ministry of Education and Research (BMBF) within the framework of the EU Joint Programming Initiative 'A Healthy Diet for a Healthy Life'
Merck Foundation/Society of Epidemiological Research
National Institute on Aging (NIA)
National Institute of Neurological Disorders and Stroke (NINDS)
NHLBI