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

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Prokic , I , Lahousse , L , de Vries , M , Liu , J , Kalaoja , M , Vonk , J M , van der Plaat , D A , van Diemen , C C , van der Spek , A , Zhernakova , A , Fu , J , Ghanbari , M , Ala-Korpela , M , Kettunen , J , Havulinna , A S , Perola , M , Salomaa , V , Lind , L , Arnlov , J , Stricker , B H C , Brusselle , G G , Boezen , H M , van Duijn , C M & Amin , N 2020 , ' A cross-omics integrative study of metabolic signatures of chronic obstructive pulmonary disease ' , BMC Pulmonary Medicine , vol. 20 , no. 1 , 193 . https://doi.org/10.1186/s12890-020-01222-7

Title: A cross-omics integrative study of metabolic signatures of chronic obstructive pulmonary disease
Author: Prokic, Ivana; Lahousse, Lies; de Vries, Maaike; Liu, Jun; Kalaoja, Marita; Vonk, Judith M.; van der Plaat, Diana A.; van Diemen, Cleo C.; van der Spek, Ashley; Zhernakova, Alexandra; Fu, Jingyuan; Ghanbari, Mohsen; Ala-Korpela, Mika; Kettunen, Johannes; Havulinna, Aki S.; Perola, Markus; Salomaa, Veikko; Lind, Lars; Arnlov, Johan; Stricker, Bruno H. C.; Brusselle, Guy G.; Boezen, H. Marike; van Duijn, Cornelia M.; Amin, Najaf
Contributor: University of Helsinki, Medicum
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2020-07-16
Language: eng
Number of pages: 10
Belongs to series: BMC Pulmonary Medicine
ISSN: 1471-2466
URI: http://hdl.handle.net/10138/319067
Abstract: 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 x 10(- 4)in the discovery and OR = 1.30,P = 1.8 x 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.
Subject: COPD
Metabolomics
Mendelian randomization
Glycoprotein acetyls
Biomarkers
ACUTE-PHASE PROTEINS
LUNG-FUNCTION
RISK-FACTORS
GLYCOPROTEIN
BIOMARKER
IDENTIFY
TESTS
GLYCA
LOCI
3121 Internal medicine
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