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Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity

Author

Listed:
  • Peter K. Joshi

    (University of Edinburgh)

  • Nicola Pirastu

    (University of Edinburgh)

  • Katherine A. Kentistou

    (University of Edinburgh
    University of Edinburgh)

  • Krista Fischer

    (University of Tartu, University of Tartu)

  • Edith Hofer

    (Medical University of Graz
    Medical University of Graz)

  • Katharina E. Schraut

    (University of Edinburgh
    University of Edinburgh)

  • David W. Clark

    (University of Edinburgh)

  • Teresa Nutile

    (Institute of Genetics and Biophysics “A. Buzzati-Traverso” - CNR)

  • Catriona L. K. Barnes

    (University of Edinburgh)

  • Paul R. H. J. Timmers

    (University of Edinburgh)

  • Xia Shen

    (University of Edinburgh
    Karolinska Institutet)

  • Ilaria Gandin

    (University of Trieste
    IRCCS “Burlo Garofolo”)

  • Aaron F. McDaid

    (Lausanne University Hospital
    Swiss Institute of Bioinformatics)

  • Thomas Folkmann Hansen

    (Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Mental Health Services Copenhagen
    The Lundbeck Foundation Initiative for Integrative Psychiatric Research)

  • Scott D. Gordon

    (QIMR Berghofer Institute of Medical Research)

  • Franco Giulianini

    (Brigham and Women’s Hospital)

  • Thibaud S. Boutin

    (University of Edinburgh, Western General Hospital)

  • Abdel Abdellaoui

    (Vrije Universiteit, Amsterdam, Amsterdam Public Health Institute (APH))

  • Wei Zhao

    (University of Michigan)

  • Carolina Medina-Gomez

    (Erasmus University Medical Center
    Erasmus University Medical Center)

  • Traci M. Bartz

    (University of Washington)

  • Stella Trompet

    (Leiden University Medical Center
    Leiden University Medical Center)

  • Leslie A. Lange

    (University of Colorado Denver, Anschutz Medical Campus)

  • Laura Raffield

    (University of North Carolina)

  • Ashley Spek

    (Erasmus University Medical Center)

  • Tessel E. Galesloot

    (Radboud university medical center)

  • Petroula Proitsi

    (University College London)

  • Lisa R. Yanek

    (Johns Hopkins University School of Medicine)

  • Lawrence F. Bielak

    (University of Michigan)

  • Antony Payton

    (The University of Manchester)

  • Federico Murgia

    ((Affiliated Institute of the University of Lübeck, Lübeck, Germany))

  • Maria Pina Concas

    (National Research Council of Italy)

  • Ginevra Biino

    (National Research Council of Italy)

  • Salman M. Tajuddin

    (National Institutes of Health)

  • Ilkka Seppälä

    (University of Tampere)

  • Najaf Amin

    (Erasmus University Medical Center)

  • Eric Boerwinkle

    (University of Texas)

  • Anders D. Børglum

    (The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Aarhus University
    Aarhus University)

  • Archie Campbell

    (University of Edinburgh)

  • Ellen W. Demerath

    (University of Minnesota)

  • Ilja Demuth

    (Universitätsmedizin Berlin
    Universitätsmedizin Berlin
    Universitätsmedizin Berlin)

  • Jessica D. Faul

    (University of Michigan)

  • Ian Ford

    (University of Glasgow)

  • Alessandro Gialluisi

    (IRCCS Neuromed)

  • Martin Gögele

    ((Affiliated Institute of the University of Lübeck, Lübeck, Germany))

  • MariaElisa Graff

    (University of North Carolina)

  • Aroon Hingorani

    (University College London)

  • Jouke-Jan Hottenga

    (Vrije Universiteit, Amsterdam, Amsterdam Public Health Institute (APH))

  • David M. Hougaard

    (The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    Statens Serum Institut)

  • Mikko A. Hurme

    (University of Tampere)

  • M. Arfan Ikram

    (Erasmus University Medical Center)

  • Marja Jylhä

    (University of Tampere)

  • Diana Kuh

    (University College London)

  • Lannie Ligthart

    (Vrije Universiteit, Amsterdam, Amsterdam Public Health Institute (APH))

  • Christina M. Lill

    (University of Lübeck)

  • Ulman Lindenberger

    (Center for Lifespan Psychology, Max Planck Institute for Human Development
    Max Planck UCL Centre for Computational Psychiatry and Ageing Research)

  • Thomas Lumley

    (University of Auckland)

  • Reedik Mägi

    (University of Tartu, University of Tartu)

  • Pedro Marques-Vidal

    (Lausanne University Hospital)

  • Sarah E. Medland

    (QIMR Berghofer Institute of Medical Research)

  • Lili Milani

    (University of Tartu, University of Tartu)

  • Reka Nagy

    (University of Edinburgh, Western General Hospital)

  • William E. R. Ollier

    (University of Manchester)

  • Patricia A. Peyser

    (University of Michigan)

  • Peter P. Pramstaller

    ((Affiliated Institute of the University of Lübeck, Lübeck, Germany))

  • Paul M. Ridker

    (Brigham and Women’s Hospital
    TH Chan School of Public Health, Harvard Medical School)

  • Fernando Rivadeneira

    (Erasmus University Medical Center
    Erasmus University Medical Center)

  • Daniela Ruggiero

    (Institute of Genetics and Biophysics “A. Buzzati-Traverso” - CNR)

  • Yasaman Saba

    (Medical University of Graz)

  • Reinhold Schmidt

    (Medical University of Graz)

  • Helena Schmidt

    (Medical University of Graz)

  • P. Eline Slagboom

    (Leiden University Medical Center)

  • Blair H. Smith

    (University of Dundee)

  • Jennifer A. Smith

    (University of Michigan
    University of Michigan)

  • Nona Sotoodehnia

    (University of Washington)

  • Elisabeth Steinhagen-Thiessen

    (Universitätsmedizin Berlin)

  • Frank J. A. Rooij

    (Erasmus University Medical Center)

  • André L. Verbeek

    (Radboud university medical center)

  • Sita H. Vermeulen

    (Radboud university medical center)

  • Peter Vollenweider

    (Lausanne University Hospital)

  • Yunpeng Wang

    (The Lundbeck Foundation Initiative for Integrative Psychiatric Research
    University of Oslo)

  • Thomas Werge

    (Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Mental Health Services Copenhagen
    The Lundbeck Foundation Initiative for Integrative Psychiatric Research)

  • John B. Whitfield

    (QIMR Berghofer Institute of Medical Research)

  • Alan B. Zonderman

    (National Institutes of Health)

  • Terho Lehtimäki

    (University of Tampere)

  • Michele K. Evans

    (National Institutes of Health)

  • Mario Pirastu

    (National Research Council of Italy)

  • Christian Fuchsberger

    ((Affiliated Institute of the University of Lübeck, Lübeck, Germany))

  • Lars Bertram

    (University of Lübeck
    Imperial College)

  • Neil Pendleton

    (University of Manchester)

  • Sharon L. R. Kardia

    (University of Michigan)

  • Marina Ciullo

    (Institute of Genetics and Biophysics “A. Buzzati-Traverso” - CNR
    IRCCS Neuromed)

  • Diane M. Becker

    (Johns Hopkins University School of Medicine)

  • Andrew Wong

    (University College London)

  • Bruce M. Psaty

    (University of Washington
    Kaiser Permanente Washington Health Research Institute)

  • Cornelia M. Duijn

    (Erasmus University Medical Center)

  • James G. Wilson

    (University of Mississippi Medical Center)

  • J. Wouter Jukema

    (Leiden University Medical Center)

  • Lambertus Kiemeney

    (Radboud university medical center)

  • André G. Uitterlinden

    (Erasmus University Medical Center
    Erasmus University Medical Center)

  • Nora Franceschini

    (University of North Carolina)

  • Kari E. North

    (University of North Carolina)

  • David R. Weir

    (University of Michigan)

  • Andres Metspalu

    (University of Tartu, University of Tartu)

  • Dorret I. Boomsma

    (Vrije Universiteit, Amsterdam, Amsterdam Public Health Institute (APH))

  • Caroline Hayward

    (University of Edinburgh, Western General Hospital)

  • Daniel Chasman

    (Brigham and Women’s Hospital
    TH Chan School of Public Health, Harvard Medical School)

  • Nicholas G. Martin

    (QIMR Berghofer Institute of Medical Research)

  • Naveed Sattar

    (University of Glasgow)

  • Harry Campbell

    (University of Edinburgh)

  • Tōnu Esko

    (University of Tartu, University of Tartu
    Broad Institute)

  • Zoltán Kutalik

    (Lausanne University Hospital
    Swiss Institute of Bioinformatics)

  • James F. Wilson

    (University of Edinburgh
    University of Edinburgh, Western General Hospital)

Abstract

Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents’ survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.

Suggested Citation

  • Peter K. Joshi & Nicola Pirastu & Katherine A. Kentistou & Krista Fischer & Edith Hofer & Katharina E. Schraut & David W. Clark & Teresa Nutile & Catriona L. K. Barnes & Paul R. H. J. Timmers & Xia Sh, 2017. "Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00934-5
    DOI: 10.1038/s41467-017-00934-5
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