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A metabolic profile of all-cause mortality risk identified in an observational study of 44,168 individuals

Author

Listed:
  • Joris Deelen

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

  • Johannes Kettunen

    (National Institute for Health and Welfare
    Computational Medicine, Center for Life Course Health Research and Biocenter Oulu, University of Oulu)

  • Krista Fischer

    (University of Tartu)

  • Ashley van der Spek

    (Erasmus Medical Center)

  • Stella Trompet

    (Leiden University Medical Center
    Leiden University Medical Center)

  • Gabi Kastenmüller

    (Helmholtz Zentrum München
    Ingolstaedter Landstraße 1
    King’s College London, St Thomas’ Hospital)

  • Andy Boyd

    (University of Bristol)

  • Jonas Zierer

    (Helmholtz Zentrum München
    King’s College London, St Thomas’ Hospital
    Novartis Campus)

  • Erik B. van den Akker

    (Leiden University Medical Center
    Delft University of Technology)

  • Mika Ala-Korpela

    (Computational Medicine, Center for Life Course Health Research and Biocenter Oulu, University of Oulu
    Baker Heart and Diabetes Institute
    University of Bristol
    University of Bristol)

  • Najaf Amin

    (Erasmus Medical Center)

  • Ayse Demirkan

    (University of Surrey
    University Medical Center Groningen)

  • Mohsen Ghanbari

    (Erasmus Medical Center
    Mashhad University of Medical Sciences)

  • Diana van Heemst

    (Leiden University Medical Center)

  • M. Arfan Ikram

    (Erasmus Medical Center
    Erasmus Medical Center
    Erasmus Medical Center)

  • Jan Bert van Klinken

    (Leiden University Medical Center
    Leiden University Medical Center)

  • Simon P. Mooijaart

    (Leiden University Medical Center)

  • Annette Peters

    (Ingolstaedter Landstraße 1
    Helmholtz Zentrum München)

  • Veikko Salomaa

    (National Institute for Health and Welfare)

  • Naveed Sattar

    (University of Glasgow)

  • Tim D. Spector

    (King’s College London, St Thomas’ Hospital)

  • Henning Tiemeier

    (Erasmus Medical Center
    Erasmus University Medical Center-Sophia Children’s Hospital)

  • Aswin Verhoeven

    (Leiden University Medical Center)

  • Melanie Waldenberger

    (Helmholtz Zentrum München
    Helmholtz Zentrum München)

  • Peter Würtz

    (Nightingale Health Ltd.)

  • George Davey Smith

    (University of Bristol)

  • Andres Metspalu

    (University of Tartu
    University of Tartu)

  • Markus Perola

    (University of Helsinki
    University of Helsinki)

  • Cristina Menni

    (King’s College London, St Thomas’ Hospital)

  • Johanna M. Geleijnse

    (Wageningen University)

  • Fotios Drenos

    (University of Bristol
    Brunel University London)

  • Marian Beekman

    (Leiden University Medical Center)

  • J. Wouter Jukema

    (Leiden University Medical Center)

  • Cornelia M. van Duijn

    (Erasmus Medical Center
    Leiden University)

  • P. Eline Slagboom

    (Leiden University Medical Center)

Abstract

Predicting longer-term mortality risk requires collection of clinical data, which is often cumbersome. Therefore, we use a well-standardized metabolomics platform to identify metabolic predictors of long-term mortality in the circulation of 44,168 individuals (age at baseline 18–109), of whom 5512 died during follow-up. We apply a stepwise (forward-backward) procedure based on meta-analysis results and identify 14 circulating biomarkers independently associating with all-cause mortality. Overall, these associations are similar in men and women and across different age strata. We subsequently show that the prediction accuracy of 5- and 10-year mortality based on a model containing the identified biomarkers and sex (C-statistic = 0.837 and 0.830, respectively) is better than that of a model containing conventional risk factors for mortality (C-statistic = 0.772 and 0.790, respectively). The use of the identified metabolic profile as a predictor of mortality or surrogate endpoint in clinical studies needs further investigation.

Suggested Citation

  • Joris Deelen & Johannes Kettunen & Krista Fischer & Ashley van der Spek & Stella Trompet & Gabi Kastenmüller & Andy Boyd & Jonas Zierer & Erik B. van den Akker & Mika Ala-Korpela & Najaf Amin & Ayse D, 2019. "A metabolic profile of all-cause mortality risk identified in an observational study of 44,168 individuals," Nature Communications, Nature, vol. 10(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11311-9
    DOI: 10.1038/s41467-019-11311-9
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    Cited by:

    1. Shiyu Zhang & Zheng Wang & Yijing Wang & Yixiao Zhu & Qiao Zhou & Xingxing Jian & Guihu Zhao & Jian Qiu & Kun Xia & Beisha Tang & Julian Mutz & Jinchen Li & Bin Li, 2024. "A metabolomic profile of biological aging in 250,341 individuals from the UK Biobank," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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