Omic risk scores are associated with COPD-related traits across three cohorts

Background: Chronic obstructive pulmonary disease (COPD) exhibits marked heterogeneity in lung function decline, mortality, exacerbations, and other disease-related outcomes. Omic risk scores (ORS) estimate the cumulative contribution of omics, such as the transcriptome, proteome, and metabolome, to a particular trait. This study evaluates the predictive value of ORS for COPD-related traits in both smoking-enriched and general population cohorts. Methods: ORS were developed and tested in 3,339 participants of Genetic Epidemiology of COPD (COPDGene) with blood RNA-sequencing, proteomic, and metabolomic. Single- and multi-omic risk scores were trained 24 cross-sectional and five longitudinal traits using 80% of the data, focusing on disease severity, exacerbations, and traits from spirometry and computed tomography scans. Multivariable models were used to test ORS associations with outcomes in remaining COPDGene participants and externally validated in SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS) (n = 2,177) and Multi-Ethnic Study of Atherosclerosis (MESA) (n = 1,000). Results: -value < 0·05). One of 15 longitudinal ORS was associated with changes in trait values between COPDGene visits. Significant associations were observed for all 38 cross-sectional ORS tested in SPIROMICS and for 16 of 24 in MESA. Proteomic and metabolomic risk scores generally displayed stronger associations than transcriptomic scores. Discussion: Blood-based ORS can predict cross-sectional and future COPD-related traits in both smoking-enriched and general population cohorts.

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Publication Details

Journal
Respiratory Research
Published
2026-09-04
DOI
https://doi.org/10.1186/s12931-026-03890-1
Citations
2
Primary Topic
Chronic Obstructive Pulmonary Disease (COPD) Research
Type
article
Field-Weighted Citation Impact
10.81

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article

Omic risk scores are associated with COPD-related traits across three cohorts

Daniel E. Guzman, Stephanie A. Christenson, Peter Durda, Brian D. Hobbs et al.
2 citations
Respiratory Research
Chronic Obstructive Pulmonary Disease (COPD) Research
10.81
article

Omic risk scores are associated with COPD-related traits across three cohorts

Daniel E. Guzman, Stephanie A. Christenson, Peter Durda, Brian D. Hobbs, Russell P. Bowler, Katherine Pratte, Katerina Kechris, Usman A. Tahir, Tess D. Pottinger, R. Graham Barr, Thomas W. Blackwell, Victor E. Ortega, Ani Manichaikul, Dawn L. DeMeo, Luciana B. Vargas, Jeffrey L. Curtis, Elizabeth C. Oelsner, Clary B. Clish, Kristin Ardlie, Ethan M. Lange, Craig P. Hersh, Deborah A. Meyers, Stacey Gabriel, Iain R. Konigsberg, Prescott G. Woodruff, Stephen S. Rich, Kristina L. Buschur, Ching‐Ti Liu, Matthew Moll, Suna Önengüt-Gümüşcü, W. Craig Johnson, Namrata Gupta, Leslie A. Lange, Kent D. Taylor, Eugene R. Bleecker, Jerome I. Rotter, Joshua D. Smith, Edwin K. Silverman, Russell P. Tracy, Michael H. Cho, Robert E. Gerszten, François Aguet, Peter J. Castaldi
article en
2 citations

Abstract

Background: Chronic obstructive pulmonary disease (COPD) exhibits marked heterogeneity in lung function decline, mortality, exacerbations, and other disease-related outcomes. Omic risk scores (ORS) estimate the cumulative contribution of omics, such as the transcriptome, proteome, and metabolome, to a particular trait. This study evaluates the predictive value of ORS for COPD-related traits in both smoking-enriched and general population cohorts. Methods: ORS were developed and tested in 3,339 participants of Genetic Epidemiology of COPD (COPDGene) with blood RNA-sequencing, proteomic, and metabolomic. Single- and multi-omic risk scores were trained 24 cross-sectional and five longitudinal traits using 80% of the data, focusing on disease severity, exacerbations, and traits from spirometry and computed tomography scans. Multivariable models were used to test ORS associations with outcomes in remaining COPDGene participants and externally validated in SubPopulations and InteRmediate Outcome Measures in COPD Study (SPIROMICS) (n = 2,177) and Multi-Ethnic Study of Atherosclerosis (MESA) (n = 1,000). Results: -value < 0·05). One of 15 longitudinal ORS was associated with changes in trait values between COPDGene visits. Significant associations were observed for all 38 cross-sectional ORS tested in SPIROMICS and for 16 of 24 in MESA. Proteomic and metabolomic risk scores generally displayed stronger associations than transcriptomic scores. Discussion: Blood-based ORS can predict cross-sectional and future COPD-related traits in both smoking-enriched and general population cohorts.

Respiratory Research
Broad Institute (US), University of Vermont (US), Brigham and Women's Hospital (US), Beth Israel Deaconess Medical Center (US), Cleveland Clinic (US), Harvard University (US), Colorado School of Public Health (US), University of California, San Francisco (US), University of Washington (US), University of Michigan (US), Columbia University Irving Medical Center (US), UCLA Medical Center (US), VA Boston Healthcare System (US), National Jewish Health (US), Mayo Clinic in Arizona (US), Duke Medical Center (US), New York Genome Center (US), Harbor–UCLA Medical Center (US), University of Virginia (US), University of Colorado Anschutz Medical Campus (US), University of Colorado Denver (US)
National Heart, Lung, and Blood Institute
Openalex Percentile: Top 3%
Chronic Obstructive Pulmonary Disease (COPD) Research
10.81
DOIOpen Access PDFOpenAlex
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