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

Author

Listed:
  • Min-A Jhun

    (University of Michigan School of Public Health
    Stanford University School of Medicine)

  • Michael Mendelson

    (National Institutes of Health
    Boston Children’s Hospital)

  • Rory Wilson

    (Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Rahul Gondalia

    (University of North Carolina)

  • Roby Joehanes

    (Harvard Medical School)

  • Elias Salfati

    (Stanford University School of Medicine)

  • Xiaoping Zhao

    (The University of Texas Health Science Center at Houston)

  • Kim Valeska Emilie Braun

    (Erasmus MC University Medical Center)

  • Anh Nguyet Do

    (University of Alabama at Birmingham)

  • Åsa K. Hedman

    (Uppsala University)

  • Tao Zhang

    (Tulane University School of Public Health and Tropical Medicine)

  • Elena Carnero-Montoro

    (King’s College London
    GENYO, Center for Genomics and Oncological Research Pfizer/University of Granada/Andalusian Regional Government)

  • Jincheng Shen

    (University of Utah)

  • Traci M. Bartz

    (University of Washington)

  • Jennifer A. Brody

    (University of Washington)

  • May E. Montasser

    (University of Maryland School of Medicine
    University of Maryland School of Medicine)

  • Jeff R. O’Connell

    (University of Maryland School of Medicine
    University of Maryland School of Medicine)

  • Chen Yao

    (National Institutes of Health)

  • Rui Xia

    (The University of Texas Health Science Center at Houston)

  • Eric Boerwinkle

    (University of Texas Health Science Center at Houston)

  • Megan Grove

    (University of Texas Health Science Center at Houston)

  • Weihua Guan

    (University of Minnesota)

  • Pfeiffer Liliane

    (Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Paula Singmann

    (Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Martina Müller-Nurasyid

    (Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    IBE, Faculty of Medicine, LMU Munich
    Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University)

  • Thomas Meitinger

    (Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University
    Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health
    Technical University Munich)

  • Christian Gieger

    (Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Annette Peters

    (Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University)

  • Wei Zhao

    (University of Michigan School of Public Health)

  • Erin B. Ware

    (University of Michigan School of Public Health
    Survey Research Center, Institute for Social Research)

  • Jennifer A. Smith

    (University of Michigan School of Public Health
    Survey Research Center, Institute for Social Research)

  • Klodian Dhana

    (Rush University Medical Center)

  • Joyce Meurs

    (Erasmus MC University Medical Center)

  • Andre Uitterlinden

    (Erasmus MC University Medical Center)

  • Mohammad Arfan Ikram

    (Erasmus MC University Medical Center)

  • Mohsen Ghanbari

    (Erasmus MC University Medical Center)

  • Deugi Zhi

    (University of Texas Health Science Center at Houston)

  • Stefan Gustafsson

    (Uppsala University)

  • Lars Lind

    (Uppsala University)

  • Shengxu Li

    (Tulane University School of Public Health and Tropical Medicine)

  • Dianjianyi Sun

    (Tulane University School of Public Health and Tropical Medicine
    Peking University Health Science Center)

  • Tim D. Spector

    (King’s College London)

  • Yii-der Ida Chen

    (Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, and Department of Pediatrics, Harbor-UCLA Medical Center)

  • Coleen Damcott

    (University of Maryland School of Medicine
    University of Maryland School of Medicine)

  • Alan R. Shuldiner

    (University of Maryland School of Medicine
    University of Maryland School of Medicine)

  • Devin M. Absher

    (HudsonAlpha Institute for Biotechnology)

  • Steve Horvath

    (University of California Los Angeles
    University of California Los Angeles)

  • Philip S. Tsao

    (Stanford University School of Medicine
    VA Palo Alto Healthcare System
    Stanford Cardiovascular Institute, Stanford University)

  • Sharon Kardia

    (University of Michigan School of Public Health)

  • Bruce M. Psaty

    (University of Washington
    Kaiser Permanente Washington Health Research Institute)

  • Nona Sotoodehnia

    (University of Washington)

  • Jordana T. Bell

    (King’s College London)

  • Erik Ingelsson

    (Stanford University School of Medicine
    Uppsala University
    Stanford Cardiovascular Institute, Stanford University
    Stanford University)

  • Wei Chen

    (Tulane University School of Public Health and Tropical Medicine)

  • Abbas Dehghan

    (Erasmus MC University Medical Center
    Imperial College)

  • Donna K. Arnett

    (University of Alabama at Birmingham)

  • Melanie Waldenberger

    (Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Lifang Hou

    (Northwestern University)

  • Eric A. Whitsel

    (University of North Carolina
    University of North Carolina)

  • Andrea Baccarelli

    (Department of Environmental Health Sciences, Harvard T.H. Chan School of Public Health
    Columbia University Mailman School of Public Health)

  • Daniel Levy

    (National Institutes of Health
    Framingham Heart Study)

  • Myriam Fornage

    (The University of Texas Health Science Center at Houston)

  • Marguerite R. Irvin

    (University of Alabama at Birmingham)

  • Themistocles L. Assimes

    (Stanford University School of Medicine
    VA Palo Alto Healthcare System
    Stanford Cardiovascular Institute, Stanford University)

Abstract

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.

Suggested Citation

  • Min-A Jhun & Michael Mendelson & Rory Wilson & Rahul Gondalia & Roby Joehanes & Elias Salfati & Xiaoping Zhao & Kim Valeska Emilie Braun & Anh Nguyet Do & Åsa K. Hedman & Tao Zhang & Elena Carnero-Mon, 2021. "A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23899-y
    DOI: 10.1038/s41467-021-23899-y
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