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A meta-analysis of genome-wide association studies identifies multiple longevity genes

Author

Listed:
  • Joris Deelen

    (Max Planck Institute for Biology of Ageing
    Leiden University Medical Center)

  • Daniel S. Evans

    (California Pacific Medical Center Research Institute)

  • Dan E. Arking

    (Johns Hopkins University School of Medicine)

  • Niccolò Tesi

    (Vrije Universiteit Amsterdam, Amsterdam UMC
    Amsterdam UMC
    Delft University of Technology)

  • Marianne Nygaard

    (University of Southern Denmark)

  • Xiaomin Liu

    (BGI-Shenzhen
    China National Genebank, BGI-Shenzhen)

  • Mary K. Wojczynski

    (Washington University School of Medicine)

  • Mary L. Biggs

    (University of Washington
    University of Washington)

  • Ashley van der Spek

    (Erasmus MC)

  • Gil Atzmon

    (University of Haifa
    Albert Einstein College of Medicine)

  • Erin B. Ware

    (University of Michigan)

  • Chloé Sarnowski

    (Boston University School of Public Health)

  • Albert V. Smith

    (University of Michigan
    Icelandic Heart Association)

  • Ilkka Seppälä

    (Tampere University)

  • Heather J. Cordell

    (Newcastle University)

  • Janina Dose

    (Kiel University)

  • Najaf Amin

    (Erasmus MC)

  • Alice M. Arnold

    (University of Washington)

  • Kristin L. Ayers

    (Sema4, a Mount Sinai venture)

  • Nir Barzilai

    (Albert Einstein College of Medicine)

  • Elizabeth J. Becker

    (Boston University)

  • Marian Beekman

    (Leiden University Medical Center)

  • Hélène Blanché

    (Fondation Jean Dausset—CEPH)

  • Kaare Christensen

    (University of Southern Denmark
    Odense University Hospital
    Odense University Hospital)

  • Lene Christiansen

    (University of Southern Denmark
    Copenhagen University Hospital, Rigshospitalet)

  • Joanna C. Collerton

    (Newcastle University)

  • Sarah Cubaynes

    (MMDN, Univ. Montpellier, EPHE, Unité Inserm 1198, PSL Research University)

  • Steven R. Cummings

    (California Pacific Medical Center Research Institute)

  • Karen Davies

    (Newcastle University)

  • Birgit Debrabant

    (University of Southern Denmark)

  • Jean-François Deleuze

    (Fondation Jean Dausset—CEPH
    Centre National de Recherche en Génomique Humaine, CEA-Institut de Biologie François Jacob)

  • Rachel Duncan

    (Newcastle University
    Newcastle University Institute for Ageing, Newcastle University)

  • Jessica D. Faul

    (University of Michigan)

  • Claudio Franceschi

    (Lobachevsky State University of Nizhny Novgorod
    IRCCS Institute of Neurological Sciences of Bologna (ISNB))

  • Pilar Galan

    (EREN, UMR U1153 Inserm/U1125 Inra/Cnam/Paris 13, Université Paris 13, CRESS)

  • Vilmundur Gudnason

    (Icelandic Heart Association
    University of Iceland)

  • Tamara B. Harris

    (Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH)

  • Martijn Huisman

    (Vrije Universiteit Amsterdam, Amsterdam UMC
    Amsterdam Public Health Research Institute)

  • Mikko A. Hurme

    (Faculty of Medicine and Health Technology, Tampere University)

  • Carol Jagger

    (Newcastle University
    Newcastle University Institute for Ageing, Newcastle University)

  • Iris Jansen

    (Vrije Universiteit Amsterdam, Amsterdam UMC
    Vrije Universiteit Amsterdam)

  • Marja Jylhä

    (Tampere University)

  • Mika Kähönen

    (Tampere University Hospital and Finnish Cardiovascular Research Center—Tampere, Faculty of Medicine and Health Technology, Tampere University)

  • David Karasik

    (Bar Ilan University
    Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife)

  • Sharon L. R. Kardia

    (University of Michigan)

  • Andrew Kingston

    (Newcastle University
    Newcastle University Institute for Ageing, Newcastle University)

  • Thomas B. L. Kirkwood

    (Newcastle University Institute for Ageing, Newcastle University)

  • Lenore J. Launer

    (Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH)

  • Terho Lehtimäki

    (Tampere University)

  • Wolfgang Lieb

    (Kiel University)

  • Leo-Pekka Lyytikäinen

    (Tampere University)

  • Carmen Martin-Ruiz

    (Newcastle University)

  • Junxia Min

    (Zhejiang University)

  • Almut Nebel

    (Kiel University)

  • Anne B. Newman

    (University of Pittsburgh)

  • Chao Nie

    (BGI-Shenzhen)

  • Ellen A. Nohr

    (University of Southern Denmark)

  • Eric S. Orwoll

    (Oregon Health Sciences University)

  • Thomas T. Perls

    (Boston University School of Medicine)

  • Michael A. Province

    (Washington University School of Medicine)

  • Bruce M. Psaty

    (University of Washington
    University of Washington
    University of Washington
    Kaiser Permanente Washington Health Research Institute)

  • Olli T. Raitakari

    (Turku University Hospital
    University of Turku)

  • Marcel J. T. Reinders

    (Delft University of Technology)

  • Jean-Marie Robine

    (MMDN, Univ. Montpellier, EPHE, Unité Inserm 1198, PSL Research University
    CERMES3, UMR CNRS 8211—Unité Inserm 988—EHESS—Université Paris Descartes)

  • Jerome I. Rotter

    (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
    Harbor-UCLA Medical Center)

  • Paola Sebastiani

    (Boston University School of Public Health)

  • Jennifer Smith

    (University of Michigan
    University of Michigan)

  • Thorkild I. A. Sørensen

    (University of Copenhagen
    Bristol University)

  • Kent D. Taylor

    (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
    Harbor-UCLA Medical Center)

  • André G. Uitterlinden

    (Erasmus MC
    Erasmus MC)

  • Wiesje van der Flier

    (Vrije Universiteit Amsterdam, Amsterdam UMC
    Vrije Universiteit Amsterdam, Amsterdam UMC)

  • Sven J. van der Lee

    (Vrije Universiteit Amsterdam, Amsterdam UMC
    Amsterdam UMC)

  • Cornelia M. van Duijn

    (Erasmus MC
    University of Oxford)

  • Diana van Heemst

    (Leiden University Medical Center)

  • James W. Vaupel

    (Max Planck Institute for Demographic Research)

  • David Weir

    (University of Michigan)

  • Kenny Ye

    (Albert Einstein College of Medicine)

  • Yi Zeng

    (Peking University
    Medical School of Duke University)

  • Wanlin Zheng

    (California Pacific Medical Center Research Institute)

  • Henne Holstege

    (Vrije Universiteit Amsterdam, Amsterdam UMC
    Amsterdam UMC
    Delft University of Technology)

  • Douglas P. Kiel

    (Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife
    Beth Israel Deaconess Medical Center and Harvard Medical School
    Broad Institute of MIT & Harvard)

  • Kathryn L. Lunetta

    (Boston University School of Public Health)

  • P. Eline Slagboom

    (Leiden University Medical Center)

  • Joanne M. Murabito

    (NHLBI’s and Boston University’s Framingham Heart Study
    Boston University School of Medicine)

Abstract

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.

Suggested Citation

  • Joris Deelen & Daniel S. Evans & Dan E. Arking & Niccolò Tesi & Marianne Nygaard & Xiaomin Liu & Mary K. Wojczynski & Mary L. Biggs & Ashley van der Spek & Gil Atzmon & Erin B. Ware & Chloé Sarnowski , 2019. "A meta-analysis of genome-wide association studies identifies multiple longevity genes," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11558-2
    DOI: 10.1038/s41467-019-11558-2
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    Cited by:

    1. Kalmijn, Matthijs, 2022. "Intergenerational transmission of health behaviors in a changing demographic context: The case of smoking and alcohol consumption," Social Science & Medicine, Elsevier, vol. 296(C).
    2. Kejun Ying & José P. Castro & Anastasia V. Shindyapina & Alexander Tyshkovskiy & Mahdi Moqri & Ludger J. E. Goeminne & Sofiya Milman & Zhengdong D. Zhang & Nir Barzilai & Vadim N. Gladyshev, 2024. "Depletion of loss-of-function germline mutations in centenarians reveals longevity genes," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

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