University of Oulu

Prokić, I., Lahousse, L., de Vries, M. et al. A cross-omics integrative study of metabolic signatures of chronic obstructive pulmonary disease. BMC Pulm Med 20, 193 (2020).

A cross-omics integrative study of metabolic signatures of chronic obstructive pulmonary disease

Saved in:
Author: Prokić, Ivana1; Lahousse, Lies1,2; de Vries, Maaike3,4;
Organizations: 1Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
2Department of Bioanalysis, Pharmaceutical Care Unit, Ghent University, Ghent, Belgium
3Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
4Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
5Nuffield Department of Population Health, University of Oxford, Oxford, UK
6Computational Medicine department, Center for Life Course Health Research, Biocenter Oulu, University of Oulu, Oulu, Finland
7National Heart and Lung Institute, Imperial College London, London, UK
8Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
9Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
10Department of Genetics, School of Medicine,, Mashhad University of Medical Sciences, Mashhad, Iran
11NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
12Finnish Institute for Health and Welfare, Helsinki, Finland
13Molecular Metabolism Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
14Department of Medical Sciences, Uppsala University, Uppsala, Sweden
15Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Huddinge, Sweden
16School of Health and Social Sciences, Dalarna University, Falun, Sweden
17Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
18Department of Respiratory Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.5 MB)
Persistent link:
Language: English
Published: Springer Nature, 2020
Publish Date: 2020-12-02


Background: Chronic obstructive pulmonary disease (COPD) is a common lung disorder characterized by persistent and progressive airflow limitation as well as systemic changes. Metabolic changes in blood may help detect COPD in an earlier stage and predict prognosis.

Methods: We conducted a comprehensive study of circulating metabolites, measured by proton Nuclear Magnetic Resonance Spectroscopy, in relation with COPD and lung function. The discovery sample consisted of 5557 individuals from two large population-based studies in the Netherlands, the Rotterdam Study and the Erasmus Rucphen Family study. Significant findings were replicated in 12,205 individuals from the Lifelines-DEEP study, FINRISK and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) studies. For replicated metabolites further investigation of causality was performed, utilizing genetics in the Mendelian randomization approach.

Results: There were 602 cases of COPD and 4955 controls used in the discovery meta-analysis. Our logistic regression results showed that higher levels of plasma Glycoprotein acetyls (GlycA) are significantly associated with COPD (OR = 1.16, P = 5.6 × 10⁻⁴ in the discovery and OR = 1.30, P = 1.8 × 10⁻⁶ in the replication sample). A bi-directional two-sample Mendelian randomization analysis suggested that circulating blood GlycA is not causally related to COPD, but that COPD causally increases GlycA levels. Using the prospective data of the same sample of Rotterdam Study in Cox-regression, we show that the circulating GlycA level is a predictive biomarker of COPD incidence (HR = 1.99, 95%CI 1.52–2.60, comparing those in the highest and lowest quartile of GlycA) but is not significantly associated with mortality in COPD patients (HR = 1.07, 95%CI 0.94–1.20).

Conclusions: Our study shows that circulating blood GlycA is a biomarker of early COPD pathology.

see all

Series: BMC pulmonary medicine
ISSN: 1471-2466
ISSN-E: 1471-2466
ISSN-L: 1471-2466
Volume: 20
Issue: 1
Article number: 193
DOI: 10.1186/s12890-020-01222-7
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3121 General medicine, internal medicine and other clinical medicine
Funding: This work was performed within the framework of the BBMRI Metabolomics Consortium funded by BBMRI-NL, a research infrastructure financed by the Dutch government (NWO, grant nr 184.021.007 and 184033111). DvdP and NA were supported by grant number of Lung Foundation Netherlands (Longfonds). The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The ERF study as a part of EUROSPAN (European Special Populations Research Network) was supported by European Commission FP6 STRP grant number 018947 (LSHG-CT-2006-01947) and also received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013)/grant agreement HEALTH-F4–2007-201413 by the European Commission under the programme “Quality of Life and Management of the Living Resources” of 5th Framework Programme (no. QLG2-CT-2002-01254). The ERF study was further supported by ENGAGE consortium and CMSB. High-throughput analysis of the ERF data was supported by joint grant from Netherlands Organization for Scientific Research and the Russian Foundation for Basic Research (NWO-RFBR 047.017.043). LLDEEP was funded by the Netherlands Heart Foundation (IN-CONTROL CVON grant 2012–03 to A.Z. and J.F.); by the Netherlands Organization for Scientific Research (NWO) (NWO-VIDI 864.13.013 to JF, NWO-VIDI 016.178.056 to AZ, and by the European Research Council (ERC) (ERC Starting Grant 715772) to AZ. AZ also holds a Rosalind Franklin Fellowship from the University of Groningen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. FINRISK surveys are mainly funded by the budgetary funds of the National Institute for Health and Welfare. Additional funding has been obtained from the Finnish Academy (#139635 and 118065) and from domestic foundations, such as the Finnish Foundation for Cardiovascular Research (to VS). JK was supported through funds from the Academy of Finland (grant numbers 297338 and 307247) and Novo Nordisk Fonden (grant number NNF17OC0026062). MAK and JK are funded by a research grant from the Sigrid Juselius Foundation, Finland. PIVUS study was funded by Uppsala University Hospital.
Academy of Finland Grant Number: 297338
Detailed Information: 297338 (Academy of Finland Funding decision)
307247 (Academy of Finland Funding decision)
Copyright information: © The Author(s). 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.