Gene Coexpression Networks in Whole Blood Implicate Multiple Interrelated Molecular Pathways in Obesity in People with Asthma.

Autor: Croteau-Chonka DC; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA., Chen Z; Division of Environmental Health, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Barnes KC; Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA., Barraza-Villarreal A; National Institute of Public Health, Cuernavaca, Morelos, México., Celedón JC; Division of Pulmonary Medicine, Allergy and Immunology, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Gauderman WJ; Division of Biostatistics, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Gilliland FD; Division of Environmental Health, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Krishnan JA; Division of Pulmonary, Critical Care, Sleep, and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA., Liu AH; Division of Allergy and Clinical Immunology, Department of Pediatrics, National Jewish Health and University of Colorado School of Medicine, Denver, Colorado, USA., London SJ; Division of Intramural Research, Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, North Carolina, USA., Martinez FD; Arizona Respiratory Center and BIO5 Institute, University of Arizona, Tucson, Arizona, USA., Millstein J; Division of Biostatistics, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Naureckas ET; Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, Illinois, USA., Nicolae DL; Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.; Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, Illinois, USA.; Department of Statistics, University of Chicago, Chicago, Illinois, USA., White SR; Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, Illinois, USA., Ober C; Department of Human Genetics, University of Chicago, Chicago, Illinois, USA., Weiss ST; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Partners HealthCare Personalized Medicine, Partners Health Care, Boston, Massachusetts, USA., Raby BA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.; BWH Pulmonary Genetics Center, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Jazyk: angličtina
Zdroj: Obesity (Silver Spring, Md.) [Obesity (Silver Spring)] 2018 Dec; Vol. 26 (12), pp. 1938-1948. Date of Electronic Publication: 2018 Oct 25.
DOI: 10.1002/oby.22341
Abstrakt: Objective: Asthmatic children who develop obesity through adolescence have poorer disease outcomes compared with those who do not. This study aimed to characterize the biology of childhood asthma complicated by adult obesity.
Methods: Gene expression networks are powerful statistical tools for characterizing human disease that leverage the putative coregulatory relationships of genes to infer relevant biological pathways. Weighted gene coexpression network analysis of gene expression data was performed in whole blood from 514 adult asthmatic subjects. Then, module preservation and association replication analyses were performed in 418 subjects from two independent asthma cohorts (one pediatric and one adult).
Results: A multivariate model was identified in which three gene coexpression network modules were associated with incident obesity in the discovery cohort (each P < 0.05). Two module memberships were enriched for genes in pathways related to platelets, integrins, extracellular matrix, smooth muscle, NF-κB signaling, and Hedgehog signaling. The network structures of each of the obesity modules were significantly preserved in both replication cohorts (permutation P = 9.999E-05). The corresponding module gene sets were significantly enriched for differential expression in subjects with obesity in both replication cohorts (each P < 0.05).
Conclusions: The gene coexpression network profiles thus implicate multiple interrelated pathways in the biology of an important endotype of asthma with obesity.
(© 2018 The Obesity Society.)
Databáze: MEDLINE
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