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Pathway analysis of a genome-wide gene by air pollution interaction study in asthmatic children.
- Source :
-
Journal of exposure science & environmental epidemiology [J Expo Sci Environ Epidemiol] 2019 Jun; Vol. 29 (4), pp. 539-547. Date of Electronic Publication: 2019 Apr 26. - Publication Year :
- 2019
-
Abstract
- 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 (NO <subscript>2</subscript> ) and carbon monoxide (CO) interaction on lung function and to identify biological pathways involved.<br />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 FEV <subscript>1</subscript> 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.<br />Results: Two SNPs near the EPHA3 (rs13090972 and rs958144) and one in TXNDC8 (rs7041938) showed significant interactions with NO <subscript>2</subscript> 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 FEV <subscript>1</subscript> changes. For NO <subscript>2</subscript> -related FEV <subscript>1</subscript> responses, we identified pathways involved in cellular adhesion, oxidative stress, inflammation, and metabolic responses.<br />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.
Details
- Language :
- English
- ISSN :
- 1559-064X
- Volume :
- 29
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of exposure science & environmental epidemiology
- Publication Type :
- Academic Journal
- Accession number :
- 31028280
- Full Text :
- https://doi.org/10.1038/s41370-019-0136-3