Integrative analysis of transcriptome‐wide association study data and messenger RNA expression profiles identified candidate genes and pathways for inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is a complex disease, resulting from abnormal immune response to intestinal tract microbiota in genetically susceptible individuals. Crohn's disease and ulcerative colitis (UC) are the two major types of IBD. Transcriptome‐wide association study (TWAS) of IBD was first performed using a large‐scale genome‐wide association study summary data sets of IBD. The FUSION software was applied for TWAS, considering various tissues and cells. The genes identified by TWAS were then validated by the gene expression profiling data sets of IBD. The functional annotation and potential pathways of common differentially expressed genes were further subjected to gene ontology (GO) and pathway enrichment analysis. Integrative analysis of TWAS and messenger RNA (mRNA) expression data detected several tissues related common genes for UC, such as HLA‐DRB1 (PTWAS = 0.024; mRNA expression ratio = 1.700) and TAP2 in colon (P TWAS = 0.047; mRNA expression ratio = 2.170). Further comparing the GO enrichment analysis results of TWAS and mRNA expression data, we identified 11 common GO terms for UC, such as plasma membrane (P value = 5.08 × 10−10) in intestinal tissues and immune response (P = 0.001) in peripheral blood. We also detected several common pathways for UC, including cell adhesion molecules (P = 0.003) in intestinal tissues, IBD (P = 0.049) in whole blood and phagosome (P = 0.0003) in peripheral blood. Our study results provide novel clues for understanding the genetic mechanism of IBD.

Machine learning gene expression predicting model for ustekinumab response in patients with Crohn's disease

“…Some related genes and predictive models of IBD have been reported in previous studies using bioinformatics analysis. 25,[28][29][30][31] However, these studies focused on IBD and did not further discuss CD or UC separately. Besides, Leal et al 32 have elucidated inflammatory mediators in patients with CD who are unresponsive to anti-TNFα therapy.…”

Distinct transcriptomic signature of mRNA and microRNA in ulcerative colitis and irritable bowel syndrome

“…Transcriptome studies, including both mRNA and microRNA, have contributed to our understanding of IBD and IBS pathogenesis(7, 8). A lot of mRNAs, such as HLA-DRB1 and TAP2, have been found to be differentially expressed in the colon of UC(9). A number of miRNAs, as modulators of gene expression, have been found to be involved in the initiation, development and progression of UC, such as miR-21(10), miR-31(11).…”

The Effect of Myrmecodia pendans Ethanol Extract on Myeloperoxidase Level and Histopathological appearance in Dextran Sodium Sulfate-Induced Colitis Rat

“…2 The highest prevalence of CD and UC is in Northern Europe, North America, and England. 3 In Australia, from 2011 to 2013 the incidence of UC was around 10 per 100,000. 4 Incidence is increasing in Asia, Africa, Europe, South America, and most developing countries.…”

“…4 Incidence is increasing in Asia, Africa, Europe, South America, and most developing countries. 3 In Asia-Pacific, Crohn's and Colitis Epidemiology Study (ACCESS), from 2011 to 2013, in 8 Asian countries, the incidence of IBD ranged from 0.5 to 3 per 100,000, and UC around 1 per 100,000. 4 In Indonesia, there is still no epidemiological study on IBD, and the data are still based on hospital records.…”