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

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 Demirkan, Mohsen Ghanbari, Diana van Heemst, M. Arfan Ikram, Jan Bert van Klinken, Simon P. Mooijaart, Annette Peters, Veikko Salomaa, Naveed Sattar, Tim D. Spector, Henning Tiemeier, Aswin Verhoeven, Melanie Waldenberger, Peter Würtz, George Davey Smith, Andres Metspalu, Markus Perola, Cristina Menni, Johanna M. Geleijnse, Fotios Drenos, Marian Beekman, J. Wouter Jukema, Cornelia M. van Duijn and P. Eline Slagboom ()
Additional contact information
Joris Deelen: Leiden University Medical Center
Johannes Kettunen: National Institute for Health and Welfare
Krista Fischer: University of Tartu
Ashley van der Spek: Erasmus Medical Center
Stella Trompet: Leiden University Medical Center
Gabi Kastenmüller: Helmholtz Zentrum München
Andy Boyd: University of Bristol
Jonas Zierer: Helmholtz Zentrum München
Erik B. van den Akker: Leiden University Medical Center
Mika Ala-Korpela: Computational Medicine, Center for Life Course Health Research and Biocenter Oulu, University of Oulu
Najaf Amin: Erasmus Medical Center
Ayse Demirkan: University of Surrey
Mohsen Ghanbari: Erasmus Medical Center
Diana van Heemst: Leiden University Medical Center
M. Arfan Ikram: Erasmus Medical Center
Jan Bert van Klinken: Leiden University Medical Center
Simon P. Mooijaart: Leiden University Medical Center
Annette Peters: Ingolstaedter Landstraße 1
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
Aswin Verhoeven: Leiden University Medical Center
Melanie Waldenberger: Helmholtz Zentrum München
Peter Würtz: Nightingale Health Ltd.
George Davey Smith: University of Bristol
Andres Metspalu: University of Tartu
Markus Perola: University of Helsinki
Cristina Menni: King’s College London, St Thomas’ Hospital
Johanna M. Geleijnse: Wageningen University
Fotios Drenos: University of Bristol
Marian Beekman: Leiden University Medical Center
J. Wouter Jukema: Leiden University Medical Center
Cornelia M. van Duijn: Erasmus Medical Center
P. Eline Slagboom: Leiden University Medical Center

Nature Communications, 2019, vol. 10, issue 1, 1-8

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11311-9

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