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Cell Syst. 2015 Oct 28;1(4):293-301. doi: 10.1016/j.cels.2015.09.007. Epub 2015 Oct 22.

The Biomarker GlycA Is Associated with Chronic Inflammation and Predicts Long-Term Risk of Severe Infection.

Author information

1
Centre for Systems Genomics, School of BioSciences, The University of Melbourne, Parkville, 3010 Victoria, Australia; Department of Pathology, The University of Melbourne, Parkville, 3010 Victoria, Australia.
2
Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu 90014, Finland.
3
Centre for Systems Genomics, School of BioSciences, The University of Melbourne, Parkville, 3010 Victoria, Australia; Department of Microbiology and Immunology, The University of Melbourne, Parkville, 3010 Victoria, Australia.
4
National Institute for Health and Welfare, Helsinki 00271, Finland; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki 00014, Finland.
5
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki 00014, Finland.
6
Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu 90014, Finland; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio 70211, Finland.
7
MediCity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku, Turku 20520, Finland.
8
Department of Clinical Chemistry, Fimlab Laboratories, School of Medicine, University of Tampere, Tampere 33520, Finland.
9
National Institute for Health and Welfare, Helsinki 00271, Finland; MediCity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku, Turku 20520, Finland.
10
National Institute for Health and Welfare, Helsinki 00271, Finland.
11
Department of Clinical Physiology, University of Tampere and Tampere University Hospital, FI-33521 Tampere, Finland.
12
Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, FI-20520 Turku, Finland; Murdoch Childrens Research Institute, Parkville, 3052 Victoria, Australia.
13
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki 00014, Finland; Department of Public Health, University of Helsinki, Helsinki 00014, Finland.
14
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku 20520, Finland; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku 20520, Finland.
15
Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu 90014, Finland; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio 70211, Finland; Oulu University Hospital, Oulu 90220, Finland; Computational Medicine, School of Social and Community Medicine, University of Bristol, Bristol BS8 1TH, UK; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK.
16
Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu 90014, Finland; National Institute for Health and Welfare, Helsinki 00271, Finland; NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio 70211, Finland. Electronic address: johannes.kettunen@computationalmedicine.fi.
17
Centre for Systems Genomics, School of BioSciences, The University of Melbourne, Parkville, 3010 Victoria, Australia; Department of Pathology, The University of Melbourne, Parkville, 3010 Victoria, Australia; Department of Microbiology and Immunology, The University of Melbourne, Parkville, 3010 Victoria, Australia. Electronic address: minouye@unimelb.edu.au.

Abstract

The biomarker glycoprotein acetylation (GlycA) has been shown to predict risk of cardiovascular disease and all-cause mortality. Here, we characterize biological processes associated with GlycA by leveraging population-based omics data and health records from >10,000 individuals. Our analyses show that GlycA levels are chronic within individuals for up to a decade. In apparently healthy individuals, elevated GlycA corresponded to elevation of myriad inflammatory cytokines, as well as a gene coexpression network indicative of increased neutrophil activity, suggesting that individuals with high GlycA may be in a state of chronic inflammatory response. Accordingly, analysis of infection-related hospitalization and death records showed that increased GlycA increased long-term risk of severe non-localized and respiratory infections, particularly septicaemia and pneumonia. In total, our work demonstrates that GlycA is a biomarker for chronic inflammation, neutrophil activity, and risk of future severe infection. It also illustrates the utility of leveraging multi-layered omics data and health records to elucidate the molecular and cellular processes associated with biomarkers.

PMID:
27136058
DOI:
10.1016/j.cels.2015.09.007
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