Genome-wide sequencing studies in thousands of patients have identified up to 240 risk genetic variants associated with inflammatory bowel disease (IBD). Although some of these variants are already associated with specific genes, the underlying mechanisms behind these variants are not yet fully understood.
A colorectal cancer research group study of the Bellvitge Biomedical Research Institute (IDIBELL) and the Catalan Institute of Oncology (ICO) has implemented a Transcriptome-Wide Associated Study (TWAS) in data from patients with IBD. It is an innovative statistical approach that allows predicting the expression levels of different genes in a specific tissue from data derived from the DNA sequence.
Comparison of gene expression levels calculated by TWAS between samples of healthy individuals and those with IBD has discovered 39 new genes, the expression of which could be associated with susceptibility to suffering from the disease. In addition, the analysis considering more than 60 tissues and cell types showed 186 new candidate susceptibility genes. Finally, the study has identified 78 new candidate genes, which alteration exclusively in immune, epithelial, mesenchymal, or neuronal tissues would be associated with IBD.
The genes identified in the study published in the Journal of Crohn’s and Colitis participate in relevant molecular pathways, including pathways related to known therapies for inflammatory bowel diseases, such as tumor necrosis factor signaling.
The researchers conclude that these genes should be prioritized in subsequent functional studies and that they are the basis for future developments on genetic data-based risk prediction models and targeted therapies.
The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.
IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).