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Metabolomics Identifies Novel Blood Biomarkers of Pulmonary Function and COPD in the General Population

1
Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
2
Institute of Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, 85764 Neuherberg, Germany
3
Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC 27713, USA
4
Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA
5
Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA
6
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
7
Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München—German Research Center for Environmental Health, 85764 Neuherberg, Germany
8
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, 85764 Neuherberg, Germany
9
Weill Cornell Medicine-Qatar, Department of Physiology and Biophysics, Education City, Doha, Qatar
10
Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), 81377 Munich, Germany
11
Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-Universität, 80336 Munich, Germany
12
Discovery and Translational Sciences, Metabolon, Inc., Durham, NC 27713, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
These authors contributed equally to this work as senior authors.
Metabolites 2019, 9(4), 61; https://doi.org/10.3390/metabo9040061
Received: 8 February 2019 / Revised: 21 March 2019 / Accepted: 26 March 2019 / Published: 1 April 2019
(This article belongs to the Special Issue Metabolomics and Chronic Obstructive Lung Diseases)
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Abstract

Determination of metabolomic signatures of pulmonary function and chronic obstructive pulmonary disease (COPD) in the general population could aid in identification and understanding of early disease processes. Metabolome measurements were performed on serum from 4742 individuals (2354 African-Americans and 1529 European-Americans from the Atherosclerosis Risk in Communities study and 859 Europeans from the Cooperative Health Research in the Region of Augsburg study). We examined 368 metabolites in relation to cross-sectional measures of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), their ratio (FEV1/FVC) and COPD using multivariable regression followed by meta-analysis. At a false discovery rate of 0.05, 95 metabolites were associated with FEV1 and 100 with FVC (73 overlapping), including inverse associations with branched-chain amino acids and positive associations with glutamine. Ten metabolites were associated with FEV1/FVC and seventeen with COPD (393 cases). Enriched pathways of amino acid metabolism were identified. Associations with FEV1 and FVC were not driven by individuals with COPD. We identified novel metabolic signatures of pulmonary function and COPD in African and European ancestry populations. These may allow development of biomarkers in the general population of early disease pathogenesis, before pulmonary function has decreased to levels diagnostic for COPD. View Full-Text
Keywords: metabolome; metabolomics; chronic obstructive pulmonary disease; respiratory function tests; forced expiratory volume metabolome; metabolomics; chronic obstructive pulmonary disease; respiratory function tests; forced expiratory volume
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    Description: Primary data is available through the established application procedures for the ARIC and KORA studies. Application for KORA data can be made via the KORA Project Application Self-Service Tool, KORA.PASST, at https://epi.helmholtz-muenchen.de/.
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Yu, B.; Flexeder, C.; McGarrah, R.W., III; Wyss, A.; Morrison, A.C.; North, K.E.; Boerwinkle, E.; Kastenmüller, G.; Gieger, C.; Suhre, K.; Karrasch, S.; Peters, A.; Wagner, G.R.; Michelotti, G.A.; Mohney, R.P.; Schulz, H.; London, S.J. Metabolomics Identifies Novel Blood Biomarkers of Pulmonary Function and COPD in the General Population. Metabolites 2019, 9, 61.

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