The effects of air and transportation noise pollution-related altered blood gene expression, DNA methylation, and protein abundance levels on gastrointestinal diseases risk.

ABSTRACT

INTRODUCTION: Air pollution and transportation noise pollution has been linked to gastrointestinal (GI) diseases, but their relationship remains unclear. METHODS: We extracted the significantly modulated genes and CpG sites related to air pollution (PM2.5, PM10, and NOx) and transportation noise pollution (aircraft, railway, and traffic road noise) from previous published studies. Genome-wide methylation analysis and colocalization analysis with these CpG sites and GWAS data of GI diseases were performed to disentangle the relationship between pollution-related blood DNA methylation (DNAm) alterations and GI diseases risk. Summary-based Mendelian randomization (SMR) analysis assessed the impact of pollution-related genes on GI diseases risk across methylation, gene expression, and protein levels. Enrichment analysis investigated the implicated biological pathways and immune cell types. RESULTS: DNAm at cg00227781 [CD300A] (modulated by NOx exposure) and cg19215199 [ZMIZ1] (modulated by PM2.5 exposure) was significantly linked to increased noninfective enteritis and colitis risk, while cg08500171 [BAT2] (modulated by NOx exposure) is significantly associated with an increased gastroesophageal reflux disease (GERD) risk. Colocalization analysis provides strong evidence supporting a shared causal variant between these associations. Multi-omics levels SMR analysis revealed that pollution-modulated lower DNAm at 5 specific CpG sites were associated with increased expression of 4 genes (IL21R, EVPL, SYNGR1, and WDR46), subsequently increasing the risk of GERD, ulcerative colitis, and gastric ulcer. 7 circulating proteins coded by pollution-modulated genes were observed to be associated with 6 GI diseases risk. Enrichment analysis implicates immune and inflammatory responses, MAPK signaling, and telomere maintenance in these pollution-induced effects. CONCLUSION: We identified potential links between air and transportation noise pollution-related gene methylation, expression, and protein abundance with GI diseases risk, possibly revealing new therapeutic targets.