@article{42e3ff48b63c4b44949cc412d67b0957,
title = "Gene Coexpression Networks in Whole Blood Implicate Multiple Interrelated Molecular Pathways in Obesity in People with Asthma",
abstract = "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.",
author = "Croteau-Chonka, {Damien C.} and Zhanghua Chen and Barnes, {Kathleen C.} and Albino Barraza-Villarreal and Celed{\'o}n, {Juan C.} and Gauderman, {W. James} and Gilliland, {Frank D.} and Krishnan, {Jerry A.} and Liu, {Andrew H.} and London, {Stephanie J.} and Martinez, {Fernando D.} and Joshua Millstein and Naureckas, {Edward T.} and Nicolae, {Dan L.} and White, {Steven R.} and Carole Ober and Weiss, {Scott T.} and Raby, {Benjamin A.}",
note = "Funding Information: Funding agencies: This work was funded by the following extramural grants from the National Heart, Lung, and Blood Institute at the U.S. National Institutes of Health (NIH): RC2 HL101543 (America Recovery and Reinvestment Act “Grand Opportunity”) (BAR), R01 HL086601 (BAR), and K01 HL127265 (DCC-C). SJL was supported by the NIH Intramural Research Program at the National Institute of Environmental Health Sciences. Disclosure: JCC reports relevant financial activities outside of conducting this study (grants from Merck and GlaxoSmithKline) and nonfinancial support from Pharmavite. AHL reports relevant financial activities outside of conducting this study (personal fees from Phadia Thermofisher and Merck Sharp & Dohme) and other support from GlaxoSmithKline. FDM reports relevant financial activities outside of conducting this study (grants from Johnson & Johnson) and personal fees from Copeval and Commense, Inc. BAR reports relevant financial activities outside of conducting this study (personal fees from UpToDate, Inc). The other authors declared no conflict of interest. Author contributions: DCC-C and BAR designed the study. DCC-C performed the analyses. KCB, AB-V, JCC, WJG, FDG, JAK, AHL, SJL, FDM, JM, ETN, DLN, SRW, CO, STW, and BAR supervised the primary data generation.ZC curated additional phenotype data for analysis. DCC-C and BAR wrote the manuscript. All coauthors read and approved the final manuscript. Additional supporting information may be found in the online version of this article. Received: 3 May 2018; Accepted: 11 September 2018; Published online 25 October 2018. doi:10.1002/oby.22341 Publisher Copyright: {\textcopyright} 2018 The Obesity Society",
year = "2018",
month = dec,
doi = "10.1002/oby.22341",
language = "English (US)",
volume = "26",
pages = "1938--1948",
journal = "Obesity",
issn = "1930-7381",
publisher = "Wiley-Blackwell",
number = "12",
}