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

Scott C Ritchie; Peter Würtz; Artika P Nath; Gad Abraham; Aki S Havulinna; Liam G Fearnley; Antti-Pekka Sarin; Antti J Kangas; Pasi Soininen; Kristiina Aalto; Ilkka Seppälä; Emma Raitoharju; Marko Salmi; Mikael Maksimow; Satu Männistö; Mika Kähönen; Markus Juonala; Samuli Ripatti; Terho Lehtimäki; Sirpa Jalkanen; Markus Perola; Olli Raitakari; Veikko Salomaa; Mika Ala-Korpela; Johannes Kettunen; Michael Inouye

doi:10.1016/j.cels.2015.09.007

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

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

Authors

Scott C Ritchie¹, Peter Würtz², Artika P Nath³, Gad Abraham¹, Aki S Havulinna⁴, Liam G Fearnley¹, Antti-Pekka Sarin⁵, Antti J Kangas², Pasi Soininen⁶, Kristiina Aalto⁷, Ilkka Seppälä⁸, Emma Raitoharju⁸, Marko Salmi⁹, Mikael Maksimow⁹, Satu Männistö¹⁰, Mika Kähönen¹¹, Markus Juonala¹², Samuli Ripatti¹³, Terho Lehtimäki⁸, Sirpa Jalkanen⁷, Markus Perola⁴, Olli Raitakari¹⁴, Veikko Salomaa¹⁰, Mika Ala-Korpela¹⁵, Johannes Kettunen¹⁶, Michael Inouye¹⁷

Affiliations

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.

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

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.