title: Gene Expression Profiling in Blood Provides Reproducible Molecular Insights into Asthma Control.
abstract: 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.
  
  
  
  To identify molecular pathways and interrelated genes whose differential expression was associated with asthma control.
  
  
  
  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 CD4+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 second WB set (n = 448, acute) and two CD4 sets (n = 300, chronic; n = 77, acute).
  
  
  
  In the WB discovery 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.
  
  
  
  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).
authors: 1 Channing Division of Network Medicine and.
authors: Damien C
authors: 0000-0003-3466-1846
authors: DC
authors: Croteau-Chonka
authors: 1 Channing Division of Network Medicine and.
authors: Weiliang
authors: 0000-0002-9155-6957
authors: W
authors: Qiu
authors: 2 Arizona Respiratory Center and BIO5 Institute, University of Arizona, Tucson, Arizona.
authors: Fernando D
authors: 0000-0001-6094-2727
authors: FD
authors: Martinez
authors: 3 Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
authors: Robert C
authors: 0000-0002-1583-6025
authors: RC
authors: Strunk
authors: 4 University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors: Robert F
authors: RF
authors: Lemanske
authors: 5 Division of Allergy and Clinical Immunology, Department of Pediatrics, National Jewish Health and University of Colorado School of Medicine, Denver, Colorado.
authors: Andrew H
authors: AH
authors: Liu
authors: 6 Division of Environmental Health and.
authors: Frank D
authors: 0000-0002-9033-7269
authors: FD
authors: Gilliland
authors: 7 Division of Biostatistics, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Joshua
authors: J
authors: Millstein
authors: 7 Division of Biostatistics, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: W James
authors: WJ
authors: Gauderman
authors: 8 Department of Human Genetics.
authors: Carole
authors: C
authors: Ober
authors: 9 Division of Pulmonary, Critical Care, Sleep, and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois.
authors: Jerry A
authors: JA
authors: Krishnan
authors: 10 Section of Pulmonary and Critical Care Medicine, Department of Medicine.
authors: Steven R
authors: SR
authors: White
authors: 10 Section of Pulmonary and Critical Care Medicine, Department of Medicine.
authors: Edward T
authors: ET
authors: Naureckas
authors: 8 Department of Human Genetics.|11 Section of Genetic Medicine, Department of Medicine, and.|12 Department of Statistics, University of Chicago, Chicago, Illinois.
authors: Dan L
authors: DL
authors: Nicolae
authors: 13 Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
authors: Kathleen C
authors: KC
authors: Barnes
authors: 14 Division of Intramural Research, Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina.
authors: Stephanie J
authors: 0000-0003-4911-5290
authors: SJ
authors: London
authors: 15 National Institute of Public Health, Cuernavaca, Morelos, México; and.
authors: Albino
authors: 0000-0002-9020-4175
authors: A
authors: Barraza-Villarreal
authors: 1 Channing Division of Network Medicine and.
authors: Vincent J
authors: 0000-0003-4046-0063
authors: VJ
authors: Carey
authors: 1 Channing Division of Network Medicine and.|16 Partners HealthCare Personalized Medicine, Partners Health Care, Boston, Massachusetts.
authors: Scott T
authors: 0000-0001-7196-303X
authors: ST
authors: Weiss
authors: 1 Channing Division of Network Medicine and.|17 Pulmonary Genetics Center and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors: Benjamin A
authors: 0000-0003-2206-5748
authors: BA
authors: Raby
mesh_terms: D000328:Adult; D001249:Asthma / Q000097:blood* / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D059467:Transcriptome; D055815:Young Adult
keywords: asthma; blood; exacerbation; gene expression; genomics