Journal article

Elevated serum alpha-1 antitrypsin is a major component of GlycA-associated risk for future morbidity and mortality

Scott C Ritchie, Johannes Kettunen, Marta Brozynska, Artika P Nath, Aki S Havulinna, Satu Maennist, Markus Perola, Veikko Salomaa, Mika Ala-Korpela, Gad Abraham, Peter Wuertz, Michael Inouye

PLoS One | PUBLIC LIBRARY SCIENCE | Published : 2019

Abstract

BACKGROUND: GlycA is a nuclear magnetic resonance (NMR) spectroscopy biomarker that predicts risk of disease from myriad causes. It is heterogeneous; arising from five circulating glycoproteins with dynamic concentrations: alpha-1 antitrypsin (AAT), alpha-1-acid glycoprotein (AGP), haptoglobin (HP), transferrin (TF), and alpha-1-antichymotrypsin (AACT). The contributions of each glycoprotein to the disease and mortality risks predicted by GlycA remain unknown. METHODS: We trained imputation models for AAT, AGP, HP, and TF from NMR metabolite measurements in 626 adults from a population cohort with matched NMR and immunoassay data. Levels of AAT, AGP, and HP were estimated in 11,861 adults fr..

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Grants

Awarded by National Health and Medical Research Council (NHMRC)


Awarded by UK Medical Research Council


Awarded by British Heart Foundation


Awarded by Australian Heart Foundation


Awarded by NHMRC Early Career Fellowship


Awarded by Academy of Finland


Awarded by Novo Nordisk Foundation


Funding Acknowledgements

This study was supported by funding from National Health and Medical Research Council (NHMRC) grant APP1062227 and by the Victorian Government's Operational Infrastructure Support (OIS) program, as well as core funding from the UK Medical Research Council (MR/L003120/1), the British Heart Foundation (RG/13/13/30194; RG/18/13/33946) and the National Institute for Health Research [Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust] [.]. M.I. and S.C.R. were funded by the National Institute for Health Research [Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust] [.]. M.I. was supported by an NHMRC and Australian Heart Foundation Career Development Fellowship (no. 1061435). S.C.R. was supported by an Australian Postgraduate Award. G.A. was supported by an NHMRC Early Career Fellowship (no. 1090462). J.K. and P.W. were funded by Academy of Finland (grant numbers 297338 and 307247, 312476, and 312477) and Novo Nordisk Foundation (NNF17OC0026062 and 15998). V.S. was supported by the Finnish Foundation for Cardiovascular Research. M.A.K. was supported by the Sigrid Juselius Foundation, Finland. M.A.K. works in a Unit that is supported by the University of Bristol and UK Medical Research Council (MC_UU_12013/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.