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 organization: Medicum
Institute for Molecular Medicine Finland
Complex Disease Genetics
Faculty of Medicine
University of Helsinki
Research Programs Unit
CAMM - Research Program for Clinical and Molecular Metabolism
Date: 2020-07-16
Language: eng
Number of pages: 10
Belongs to series: BMC Pulmonary Medicine
ISSN: 1471-2466
DOI: https://doi.org/10.1186/s12890-020-01222-7
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
Mendelian randomization
Glycoprotein acetyls
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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