University of Oulu

Kananen, L., Hurme, M., Jylhä, M. et al. Circulating cell-free DNA level predicts all-cause mortality independent of other predictors in the Health 2000 survey. Sci Rep 10, 13809 (2020).

Circulating cell-free DNA level predicts all-cause mortality independent of other predictors in the Health 2000 survey

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Author: Kananen, L.1,2; Hurme, M.1,2; Jylhä, M.2,3;
Organizations: 1Faculty of Medicine and Health Technology (MET), Tampere University, Arvo Ylpön katu 34, Tampere, Finland
2Gerontology Research Center (GEREC), Tampere, Finland
3Faculty of Social Sciences (Health Sciences), Tampere University, Tampere, Finland
4Finnish Institute for Health and Welfare, Helsinki, Finland
5Department of Public Health, University of Turku and Turku University Hospital, Turku, Finland
6Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland
7Faculty of Medicine and Health Technology, Tampere University, and Finnish Cardiovascular Research Center, Tampere, Finland
8Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland
9Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland
10Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
11Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1 MB)
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Language: English
Published: Springer Nature, 2020
Publish Date: 2020-12-02


Increased levels of circulating cell-free DNA (cf-DNA) are associated with and predict poor health outcomes. However, its predictive ability for mortality in population-based samples remains understudied. We analysed the capability of cf-DNA to predict all-cause mortality and assessed whether it adds predictive value on top of the other risk factors in the Health 2000 survey (n = 1,257, 46–76 years of age, 15-years-follow-up, 18% deceased). When analysed in a multivariate model with the other factors that independently predicted mortality in the sample (age, gender, self-rated health, smoking and plasma levels of glucose and adiponectin), increases in cf-DNA levels were associated with increased risk of mortality (hazard ratio [HR] for 0.1 µg increase in cf-DNA: 1.017, 95% confidence interval [CI] 1.008–1.026, p = 0.0003). Inclusion of cf-DNA in the model improved the model fit and discrimination. Stratifying the analysis by cardiovascular disease (CVD) status indicated that cf-DNA predicted mortality equally well in individuals with (HR 1.018, 95% CI 1.008–1.026, p = 0.002) and without (HR 1.018, 95% CI 1.001–1.035, p = 0.033) CVD. In conclusion, our study indicates that cf-DNA level predicts mortality in middle-aged and older individuals, also among those with established CVD, and adds significant value to mortality prediction. Our results thus underscore the role of cf-DNA as a viable marker of health.

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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 10
Issue: 1
Article number: 13809
DOI: 10.1038/s41598-020-70526-9
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: The Health 2000 Survey was funded by the National Institute for Health and Welfare (THL), the Finnish Centre for Pensions (ETK), The Social Insurance Institution of Finland (KELA), The Local Government Pensions Institution (KEVA) and other organizations listed on the website of the survey. L.K. has been financially supported by Emil Aaltonen Foundation and Yrjö Jahnsson Foundation (Grant 20197181). T.L has been financially supported by Academy of Finland: Grant 322098; Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospitals (Grant X51001); Finnish Foundation for Cardiovascular Research; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (Grant 755320 for TAXINOMISIS and Grant 848146 TO-AITION); and Tampere University Hospital Supporting Foundation. J.J. has been financially supported by the Swedish Research Council (Grant 2018-02077), Strategic Research Program in Epidemiology at Karolinska Institutet and the Loo & Hans Osterman Foundation. Open access funding provided by Karolinska Institute.
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