Gene expression profiling in blood provides reproducible molecular insights into asthma control

Damien C. Croteau-Chonka, Weiliang Qiu, Fernando Martinez, Robert C. Strunk, Robert F. Lemanske, Andrew H. Liu, Frank D. Gilliland, Joshua Millstein, W. James Gauderman, Carole Ober, Jerry A. Krishnan, Steven R. White, Edward T. Naureckas, Dan L. Nicolae, Kathleen C. Barnes, Stephanie J. London, Albino Barraza-Villarreal, Vincent J. Carey, Scott T. Weiss, Benjamin A. Raby

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Rationale: Maintaining optimal symptom control remains the primary objective of asthma treatment. Better understanding of the biologic underpinnings of asthma control may lead to the development of improved clinical and pharmaceutical approaches. Objectives: To identify molecular pathways and interrelated genes whose differential expression was associated with asthma control. Methods: We performed gene set enrichment analyses of asthma control in 1,170 adults with asthma, each with gene expression data derived from either whole blood (WB) or unstimulated CD41 T lymphocytes (CD4), and a self-reported asthma control score representing either the preceding 6 months (chronic) or 7 days (acute). Our study comprised a discovery WB cohort (n = 245, chronic) and three independent, nonoverlapping replication cohorts: a secondWB set (n = 448, acute) and two CD4 sets (n = 300, chronic; n = 77, acute). Measurements and Main Results: In theWBdiscovery cohort, we found significant overrepresentation of genes associated with asthma control in 1,106 gene sets from the Molecular Signatures Database (false discovery rate, ,5%). Of these, 583 (53%) replicated in at least one replication cohort (false discovery rate, ,25%). Suboptimal control was associated with signatures of eosinophilic and granulocytic inflammatory signals, whereas optimal control signatures were enriched for immature lymphocytic patterns. These signatures included two related biologic processes related to activation by TREM-1 (triggering receptor expressed on myeloid cells 1) and lipopolysaccharide. Conclusions: Together, these results demonstrate the existence of specific, reproducible transcriptomic components in blood that vary with degree of asthma control and implicate a novel biologic target (TREM-1).

Original languageEnglish (US)
Pages (from-to)179-188
Number of pages10
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume195
Issue number2
DOIs
StatePublished - Jan 15 2017

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Keywords

  • Asthma
  • Blood
  • Exacerbation
  • Gene expression
  • Genomics

ASJC Scopus subject areas

  • Medicine(all)
  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Croteau-Chonka, D. C., Qiu, W., Martinez, F., Strunk, R. C., Lemanske, R. F., Liu, A. H., Gilliland, F. D., Millstein, J., Gauderman, W. J., Ober, C., Krishnan, J. A., White, S. R., Naureckas, E. T., Nicolae, D. L., Barnes, K. C., London, S. J., Barraza-Villarreal, A., Carey, V. J., Weiss, S. T., & Raby, B. A. (2017). Gene expression profiling in blood provides reproducible molecular insights into asthma control. American Journal of Respiratory and Critical Care Medicine, 195(2), 179-188. https://doi.org/10.1164/rccm.201601-0107OC