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 to those that do not. We 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 co-regulatory relationships of genes to infer relevant biological pathways. We performed weighted gene co-expression network analysis (WGCNA) of gene expression data in whole blood from 514 adult asthmatic subjects. We then performed module preservation and association replication analyses in 418 subjects from two independent asthma cohorts (one pediatric and one adult). Results: We identified a multivariate model in which three gene co-expression 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 obese asthma 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 who were obese in both replication cohorts (each P < 0.05). Conclusions: Our gene co-expression network profiles thus implicate multiple interrelated pathways in the biology of an important endotype of obese asthma.

Association between Physician-Diagnosed Asthma and Weight Status among Chinese Children: The Roles of Lifestyle Factors

“…Although it was most widely accepted that obesity or its metabolic complications constitute a risk factor for asthma and asthma morbidity, epidemiological evidence is accumulating on the reverse causal association from asthma to subsequent obesity. In addition, a recent study has identified co-expression network modules related to incident obesity among asthmatic children [31], providing biological evidence on asthma preceding the development of obesity. Coinciding with two population-based studies conducted on US children [4,7], the present results demonstrated that asthmatic children were at significantly increased risk of overweight and obesity, extending the literature with evidence from a large sample of Chinese children.…”

Comprehensive and Systematic Analysis of Gene Expression Patterns Associated with Body Mass Index

“…Leveraging regulatory relationships in system-level gene expression data can highlight biological pathways implicated in obesity and offer further insights into the biological function of these genetic variants. Recent studies have demonstrated that whole-blood transcriptome profiles are valid biological data for weight status and thus provide a more parsimonious method to investigate the functional genomics of obesity, wherein both genes and pathways are included 12–15 . To this end, we generated and integrated gene expression data of venous blood samples and clinical data for 90 individuals.…”

Effect of obesity on airway and systemic inflammation in adults with asthma: a systematic review and meta-analysis

“…The publication year ranged from 2006 to 2021. Sixteen articles (33%) were from America and Canada,33–48 14 (29%) were from Europe,49–61 11 (23%) were from Asia,62–72 five (10%) were from Australia and New Zealand,73–77 one (2%) was from Africa78 and one (2%) was from South America 79. Asthma was diagnosed by a physician and confirmed by variable airflow obstruction (airway hyper-responsiveness and/or bronchodilator reversibility) in 25 (52%) articles, physician-diagnosed in 19 (40%) articles, diagnosed as coded in a database in one (2%) article, and the method of asthma diagnosis was not reported in three (6%) articles.…”