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Updated: Jan 25, 2026

Genome-wide Analysis using ChIP to Identify Isoform-specific Gene Targets
Published on: July 7, 2010
Pathway analysis of a genome-wide gene by air pollution interaction study in asthmatic children
Despo Ierodiakonou1,2, Brent A Coull3, Antonella Zanobetti4
1Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. desierod@gmail.com.
Objectives:
We aimed to investigate the role of genetics in the respiratory response of asthmatic children to air pollution, with a genome-wide level analysis of gene by nitrogen dioxide (NO2) and carbon monoxide (CO) interaction on lung function and to identify biological pathways involved.
Methods:
We used a two-step method for fast linear mixed model computations for genome-wide association studies, exploring whether variants modify the longitudinal relationship between 4-month average pollution and post-bronchodilator FEV1 in 522 Caucasian and 88 African-American asthmatic children. Top hits were confirmed with classic linear mixed-effect models. We used the improved gene set enrichment analysis for GWAS (i-GSEA4GWAS) to identify plausible pathways.
Results:
Two SNPs near the EPHA3 (rs13090972 and rs958144) and one in TXNDC8 (rs7041938) showed significant interactions with NO2 in Caucasians but we did not replicate this locus in African-Americans. SNP-CO interactions did not reach genome-wide significance. The i-GSEA4GWAS showed a pathway linked to the HO-1/CO system to be associated with CO-related FEV1 changes. For NO2-related FEV1 responses, we identified pathways involved in cellular adhesion, oxidative stress, inflammation, and metabolic responses.
Conclusion:
The host lung function response to long-term exposure to pollution is linked to genes involved in cellular adhesion, oxidative stress, inflammatory, and metabolic pathways.
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