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GWAS of epigenetic aging rates in blood reveals a critical role for TERT

Author

Listed:
  • Ake T. Lu

    (University of California, Los Angeles)

  • Luting Xue

    (Boston University School of Public Health)

  • Elias L. Salfati

    (Stanford University School of Medicine)

  • Brian H. Chen

    (National Institute on Aging, National Institutes of Health
    National Heart, Lung and Blood Institute)

  • Luigi Ferrucci

    (National Institute on Aging, National Institutes of Health)

  • Daniel Levy

    (National Heart, Lung and Blood Institute)

  • Roby Joehanes

    (National Heart, Lung and Blood Institute)

  • Joanne M. Murabito

    (Boston University School of Medicine)

  • Douglas P. Kiel

    (Harvard Medical School)

  • Pei-Chien Tsai

    (Kings College London)

  • Idil Yet

    (Kings College London)

  • Jordana T. Bell

    (Kings College London)

  • Massimo Mangino

    (Kings College London)

  • Toshiko Tanaka

    (National Institute on Aging, National Institutes of Health)

  • Allan F. McRae

    (The University of Queensland
    The University of Queensland)

  • Riccardo E. Marioni

    (The University of Queensland
    University of Edinburgh
    University of Edinburgh)

  • Peter M. Visscher

    (The University of Queensland
    The University of Queensland)

  • Naomi R. Wray

    (The University of Queensland
    The University of Queensland)

  • Ian J. Deary

    (University of Edinburgh)

  • Morgan E. Levine

    (University of California, Los Angeles)

  • Austin Quach

    (University of California, Los Angeles)

  • Themistocles Assimes

    (Stanford University School of Medicine)

  • Philip S. Tsao

    (Stanford University School of Medicine
    VA Palo Alto Health Care System)

  • Devin Absher

    (HudsonAlpha Institute for Biotechnology)

  • James D. Stewart

    (University of North Carolina)

  • Yun Li

    (University of North Carolina
    University of North Carolina)

  • Alex P. Reiner

    (Fred Hutchinson Cancer Research Center Box 358080, WHI Clinical Coordinating Ctr/Public Health Sciences M3-A4)

  • Lifang Hou

    (Northwestern University Chicago
    Northwestern University Chicago)

  • Andrea A. Baccarelli

    (Columbia University Mailman School of Public Health)

  • Eric A. Whitsel

    (University of North Carolina
    University of North Carolina)

  • Abraham Aviv

    (University of Medicine and Dentistry, New Jersey Medical School)

  • Alexia Cardona

    (University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus)

  • Felix R. Day

    (University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus)

  • Nicholas J. Wareham

    (University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus)

  • John R. B. Perry

    (University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus)

  • Ken K. Ong

    (University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus
    University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus)

  • Kenneth Raj

    (Chemical and Environmental Hazards, Public Health England, Chilton)

  • Kathryn L. Lunetta

    (Boston University School of Public Health)

  • Steve Horvath

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

Abstract

DNA methylation age is an accurate biomarker of chronological age and predicts lifespan, but its underlying molecular mechanisms are unknown. In this genome-wide association study of 9907 individuals, we find gene variants mapping to five loci associated with intrinsic epigenetic age acceleration (IEAA) and gene variants in three loci associated with extrinsic epigenetic age acceleration (EEAA). Mendelian randomization analysis suggests causal influences of menarche and menopause on IEAA and lipoproteins on IEAA and EEAA. Variants associated with longer leukocyte telomere length (LTL) in the telomerase reverse transcriptase gene (TERT) paradoxically confer higher IEAA (P

Suggested Citation

  • Ake T. Lu & Luting Xue & Elias L. Salfati & Brian H. Chen & Luigi Ferrucci & Daniel Levy & Roby Joehanes & Joanne M. Murabito & Douglas P. Kiel & Pei-Chien Tsai & Idil Yet & Jordana T. Bell & Massimo , 2018. "GWAS of epigenetic aging rates in blood reveals a critical role for TERT," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02697-5
    DOI: 10.1038/s41467-017-02697-5
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    Cited by:

    1. Lucas A. Mavromatis & Daniel B. Rosoff & Andrew S. Bell & Jeesun Jung & Josephin Wagner & Falk W. Lohoff, 2023. "Multi-omic underpinnings of epigenetic aging and human longevity," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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