Metabolomics Identifies Novel Blood Biomarkers of Pulmonary Function and COPD in the General Population
Bing Yu,
Claudia Flexeder,
Robert W. McGarrah,
Annah Wyss,
Alanna C. Morrison,
Kari E. North,
Eric Boerwinkle,
Gabi Kastenmüller,
Christian Gieger,
Karsten Suhre,
Stefan Karrasch,
Annette Peters,
Gregory R. Wagner,
Gregory A. Michelotti,
Robert P. Mohney,
Holger Schulz,
Stephanie J. London
Affiliations
Bing Yu
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
Claudia Flexeder
Institute of Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, 85764 Neuherberg, Germany
Robert W. McGarrah
Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC 27713, USA
Annah Wyss
Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA
Alanna C. Morrison
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
Kari E. North
Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA
Eric Boerwinkle
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
Gabi Kastenmüller
Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München—German Research Center for Environmental Health, 85764 Neuherberg, Germany
Christian Gieger
Institute of Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, 85764 Neuherberg, Germany
Karsten Suhre
Weill Cornell Medicine-Qatar, Department of Physiology and Biophysics, Education City, Doha, Qatar
Stefan Karrasch
Institute of Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, 85764 Neuherberg, Germany
Annette Peters
Institute of Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, 85764 Neuherberg, Germany
Gregory R. Wagner
Discovery and Translational Sciences, Metabolon, Inc., Durham, NC 27713, USA
Gregory A. Michelotti
Discovery and Translational Sciences, Metabolon, Inc., Durham, NC 27713, USA
Robert P. Mohney
Discovery and Translational Sciences, Metabolon, Inc., Durham, NC 27713, USA
Holger Schulz
Institute of Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, 85764 Neuherberg, Germany
Stephanie J. London
Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA
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.
