title: The Biomarker GlycA Is Associated with Chronic Inflammation and Predicts Long-Term Risk of Severe Infection.
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.
authors.affiliation: 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.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Ritchie
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu 90014, Finland.
authors.forename: Peter
authors.initials: P
authors.lastname: Würtz
authors.affiliation: 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.
authors.forename: Artika P
authors.initials: AP
authors.lastname: Nath
authors.affiliation: 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.
authors.forename: Gad
authors.initials: G
authors.lastname: Abraham
authors.affiliation: National Institute for Health and Welfare, Helsinki 00271, Finland; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki 00014, Finland.
authors.forename: Aki S
authors.initials: AS
authors.lastname: Havulinna
authors.affiliation: 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.
authors.forename: Liam G
authors.initials: LG
authors.lastname: Fearnley
authors.affiliation: Institute for Molecular Medicine Finland, University of Helsinki, Helsinki 00014, Finland.
authors.forename: Antti-Pekka
authors.initials: AP
authors.lastname: Sarin
authors.affiliation: Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu 90014, Finland.
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Kangas
authors.affiliation: 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.
authors.forename: Pasi
authors.initials: P
authors.lastname: Soininen
authors.affiliation: MediCity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku, Turku 20520, Finland.
authors.forename: Kristiina
authors.initials: K
authors.lastname: Aalto
authors.affiliation: Department of Clinical Chemistry, Fimlab Laboratories, School of Medicine, University of Tampere, Tampere 33520, Finland.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Seppälä
authors.affiliation: Department of Clinical Chemistry, Fimlab Laboratories, School of Medicine, University of Tampere, Tampere 33520, Finland.
authors.forename: Emma
authors.initials: E
authors.lastname: Raitoharju
authors.affiliation: National Institute for Health and Welfare, Helsinki 00271, Finland; MediCity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku, Turku 20520, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Salmi
authors.affiliation: National Institute for Health and Welfare, Helsinki 00271, Finland; MediCity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku, Turku 20520, Finland.
authors.forename: Mikael
authors.initials: M
authors.lastname: Maksimow
authors.affiliation: National Institute for Health and Welfare, Helsinki 00271, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Männistö
authors.affiliation: Department of Clinical Physiology, University of Tampere and Tampere University Hospital, FI-33521 Tampere, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.affiliation: 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.
authors.forename: Markus
authors.initials: M
authors.lastname: Juonala
authors.affiliation: Institute for Molecular Medicine Finland, University of Helsinki, Helsinki 00014, Finland; Department of Public Health, University of Helsinki, Helsinki 00014, Finland.
authors.forename: Samuli
authors.initials: S
authors.lastname: Ripatti
authors.affiliation: Department of Clinical Chemistry, Fimlab Laboratories, School of Medicine, University of Tampere, Tampere 33520, Finland.
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.affiliation: MediCity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku, Turku 20520, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Jalkanen
authors.affiliation: National Institute for Health and Welfare, Helsinki 00271, Finland; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki 00014, Finland.
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.affiliation: 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.
authors.forename: Olli
authors.initials: O
authors.lastname: Raitakari
authors.affiliation: National Institute for Health and Welfare, Helsinki 00271, Finland.
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.affiliation: 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.
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
authors.affiliation: 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.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kettunen
authors.affiliation: 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.
authors.forename: Michael
authors.initials: M
authors.lastname: Inouye