Transcriptomic and Metabolomic Associations with Air Pollutants Exposure Mixture Among Young Adults with Childhood Asthma History

Abstract

Exposures to ambient air pollutants are well-known risk factors for childhood asthma and asthma exacerbation. It’s unknown whether different air pollutants individually or jointly affect pathophysiological mechanisms of asthma. In this study, we aim to integrate transcriptome and untargeted metabolome to identify dysregulated genetic and metabolic pathways that are associated with exposures to a mixture of ambient and traffic-related air pollutants among adults with asthma history. In this cross-sectional study, 102 young adults with childhood asthma history were enrolled from southern California in 2012. Whole blood transcriptome was measured using Illumina HumanHT-12 v4 Expression BeadChip, with 20,869 expression signatures. Serum untargeted metabolomics including 937 metabolites were analyzed using the Metabolon Ultra-high Performance Liquid Chromatography-Tandem Mass Spectrometry. Participants’ regional (NO2, O3, PM10, PM2.5) and near-roadway air pollution exposures averaged at one-month and one-year before study visit were estimated based on residential addresses. xMWAS network analysis and joint-pathway analysis were performed to identify subnetworks and genetic and metabolic pathways that were associated with air pollutants exposures adjusted for socio-characteristic covariates. Network analysis found that exposures to air pollutants mixture were connected to 357 gene markers and 92 metabolites. One-year and one-month averaged PM2.5 and NO2 exposures were associated with several amino acids related to serine, glycine, and beta-alanine metabolism. Lower serum levels of carnosine and aspartate, which were involved in beta-alanine metabolic pathway, as well as choline were also associated with worse asthma control (p<0.05). One-year and one-month averaged PM10 and one-month averaged O3 were associated with higher gene expression levels of HSPA5, LGMN, CTSL and HLA-DPB1 that are involved in antigen processing and presentation. These results indicate that various air pollutants exposure may alter genetic and metabolic pathways that affect anti-oxidative capacity and immune response and can potentially contribute to asthma-related pathophysiology.

Keywords: Air PollutionMetabolomicsGene ExpressionIntegrated Omics Asthma Network and Pathway Analysis