The genetic architecture of inflammatory bowel disease

Authors:
Publisher website
Google Scholar
Abstract
Genome-wide association studies (GWAS) have helped to understand the genetic basis and pathogenesis of inflammatory bowel disease (IBD). However, understanding the functional and clinical consequences of the associated alleles has not followed the same pace. In this review, we discuss how studying the genetic predisposition to IBD has increased our understanding about IBD pathogenesis and how epigenetics is becoming more and more important. We describe the potential clinical applications of genetics, and provide important challenges in the field and the future steps to be taken. GWAS and meta-analyses have identified 163 loci associated with IBD, and have implicated key pathways in IBD pathogenesis. Only few of the association signals correspond to nonsynonymous coding variation with a clear effect on protein function. The majority of signals involve noncoding genetic variation, of which a large part is related to gene expression changes. More recently, expression and epigenetic studies in IBD are increasingly being reported, and have shown that many effects seem to be highly cell-type specific. Predictive genetic testing will not be for the immediate future for the majority of IBD patients. However, for the subset of patients with very-early onset IBD, several causal mutations have been found. Predictive genetic panels for these adolescents presenting with a very severe disease course, and/or families with high penetrance of disease will be of benefit. Genetic, transcriptomic and epigenetic studies have offered exciting clues about IBD pathogenesis but are unlikely to provide all answers. To fully grasp the function of disease-associated genetic variants, identifying causal genes and translating this knowledge into predictive biomarkers and new treatments, we should now integrate all these disciplines.

This publication has 68 references indexed in Scilit: