Identifying chemicals associated with irritable bowel syndrome by integrating a transcriptome-wide association study with chemical-gene-interaction analysis

BACKGROUND: Irritable bowel syndrome (IBS) is a prominent functional gastrointestinal disorder, yet the precise causes and mechanisms behind it remain largely unclear. Numerous environmental compounds have been associated with the intestinal health of individuals suffering from IBS. This study sought to explore the impact of environmental chemicals on the condition of IBS. METHODS: We analyzed genome-wide association study (GWAS) data comprising 455,321 individuals of white British descent, among which 28,518 individuals with IBS underwent transcriptome-wide association study (TWAS) analysis. Reference gene expression data were sourced from tissues including the small intestine, transverse colon, sigmoid colon, whole blood, and peripheral blood. RESULTS: Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted utilizing the significant genes identified through TWAS. Additionally, protein-protein interaction network analysis was performed using the STRING database to elucidate the functions of the proteins encoded by these genes. Furthermore, chemical-related gene set enrichment analysis (CGSEA) was employed to explore the associations between environmental chemicals and IBS. In total, TWAS identified 33 significant genes (PFDR < 0.05), while CGSEA revealed 112 chemicals significantly correlated with IBS (PFDR < 0.05, |NES| > 1). Both TWAS (targeting genetic influences) and CGSEA (focusing on environmental influences) were instrumental in pinpointing chemicals associated with IBS. CONCLUSION: The results of this study enhance our comprehension of the genetic and environmental determinants associated with functional gastrointestinal disorders.