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Jhun, M.A.* ; Mendelson, M.* ; Wilson, R. ; Gondalia, R.* ; Joehanes, R.* ; Salfati, E.L.* ; Zhao, X.* ; Braun, K.V.E.* ; Do, A.N.* ; Hedman, A.K.* ; Zhang, T.* ; Carnero-Montoro, E.* ; Shen, J.* ; Bartz, T.M.* ; Brody, J.A.* ; Montasser, M.E.* ; O’Connell, J.R.* ; Yao, C.* ; Xia, R.* ; Boerwinkle, E.* ; Grove, M.* ; Guan, W.* ; Pfeiffer, L. ; Singmann, P. ; Müller-Nurasyid, M. ; Meitinger, T. ; Gieger, C. ; Peters, A. ; Zhao, W.* ; Ware, E.B.* ; Smith, J.A.* ; Dhana, K.* ; van Meurs, J.* ; Uitterlinden, A.* ; Ikram, M.A.* ; Ghanbari, M.* ; Zhi, D.* ; Gustafsson, S.* ; Lind, L.* ; Li, S.* ; Sun, D.* ; Spector, T.D.* ; Chen, Y.D.I.* ; Damcott, C.* ; Shuldiner, A.R.* ; Absher, D.M.* ; Horvath, S.* ; Tsao, P.S.* ; Kardia, S.* ; Psaty, B.M.* ; Sotoodehnia, N.* ; Bell, J.T.* ; Ingelsson, E.* ; Chen, W.* ; Dehghan, A.* ; Arnett, D.K.* ; Waldenberger, M. ; Hou, L.* ; Whitsel, E.A.* ; Baccarelli, A.* ; Levy, D.* ; Fornage, M.* ; Irvin, M.R.* ; Assimes, T.L.*

A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids.

Nat. Commun. 12:3987 (2021)

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	Open Access Gold

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Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Mendelian Randomization; Lowering Drugs; Genome-wide; Loci; Plasma; Abcg1; Normalization; Cholesterol; Biomarkers; Genetics

ISSN (print) / ISBN 2041-1723

e-ISSN 2041-1723

Journal Nature Communications

Quellenangaben Volume: 12, Issue: 1, Article Number: 3987

Publisher Nature Publishing Group

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Epidemiology II (EPI2)
Institute of Genetic Epidemiology (IGE)
Institute of Human Genetics (IHG)

Grants
NHLBI NIH HHS
National Institute on Aging (NIA)
Laughlin Family
Alpha Phi Foundation
Locke Charitable Foundation
National Heart, Lung, and Blood Institute
National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services
NHLBI
National Center for Advancing Translational Sciences, CTSI
National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC)
Swedish Research Council
Knut och Alice Wallenberg Foundation
Swedish Heart-Lung Foundation
Swedish Diabetes Foundation
Genetic Laboratory of the Department of Internal Medicine, Erasmus MC
Netherlands Organization for Scientific research (NWO)
NHLBI Broad Agency Announcement
National Institute of Environmental Health Sciences
National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services
5RC2HL102419
King's College London
National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust
National Institutes of Health
Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health
NIH National Heart, Lung, and Blood Institute
Genetic Epidemiology Network of Arteriopathy (GENOA)
German Federal Ministry of Education and Research (BMBF)
State of Bavaria
Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universitat, LMUinnovativ
German Research Foundation
ESRC
Wellcome Trust
European Community's Seventh Framework Programme (FP7/2007-2013)
R01NS087541