Multiple outcome meta-analysis of gene-expression data in inflammatory bowel disease

• Published in: Genomics (San Diego, Calif.) Calif.), 2020-03, Vol.112 (2), p.1761-1767
• Main Authors: Vennou, Konstantina E., Piovani, Daniele, Kontou, Panagiota I., Bonovas, Stefanos, Bagos, Pantelis G.
• Format: Article
• Language: English
• Subjects: Colitis, Ulcerative - genetics; Colitis, Ulcerative - metabolism; Crohn Disease - genetics; Crohn Disease - metabolism; Crohn's disease; Differentially expressed genes; Gene expression; Granzymes - genetics; Granzymes - metabolism; Humans; Interferon-gamma - genetics; Interferon-gamma - metabolism; Janus Kinases - genetics; Janus Kinases - metabolism; Microarray; Multiple outcome meta-analysis; Signal Transduction; STAT Transcription Factors - genetics; STAT Transcription Factors - metabolism; Transaminases - genetics; Transaminases - metabolism; Transcriptome; Ulcerative colitis
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1016/j.ygeno.2019.09.019

We performed a multivariate meta-analysis of microarray data in Crohn's disease (CD) and Ulcerative colitis (UC), which are the main forms of inflammatory bowel disease (IBD). They share similar symptoms but differ in the location and extent of inflammation and in complications. We identified 249 differentially expressed genes (DEGs) in CD and 38 in UC at a false discovery rate of 1%. 20 of the DEGs were common to both diseases. A multivariate test identified 260 DEGs associated with IBD, 53 of which were not found in any of the disorders. We identified important molecular pathways implicated in the pathogenesis of IBD, such as the JAK/STAT and interferon-gamma signaling pathways, genes involved in cell adhesion, apoptosis and carcinogenesis. Among others, BCAT1 and GZMB are interesting novel DEGs that deserve further investigation in experimental models. The method could also be useful to other cases of meta-analysis of gene expression data. •Multivariate meta-analysis in 4 microarray datasets containing data for 25,409 genes from 159 controls, 251 CD and 175 UC patients.•Identification of 249 statistically significant DEGs in CD and 38 in UC at an FDR of 1%. 20 of the DEGs were common to both disorders.•The multivariate test identified 260 globally significant DEGs, 53 of which were not found in any of the disorders.•Important molecular pathways implicated in the pathogenesis of IBD.•The JAK/STAT, Interferon-gamma signaling pathways, genes involved in cell adhesion, apoptosis and carcinogenesis.