Genetic studies of Crohn's disease: past, present and future

Best Pract Res Clin Gastroenterol. 2014 Jun;28(3):373-86. doi: 10.1016/j.bpg.2014.04.009. Epub 2014 May 6.


The exact aetiology of Crohn's disease is unknown, though it is clear from early epidemiological studies that a combination of genetic and environmental risk factors contributes to an individual's disease susceptibility. Here, we review the history of gene-mapping studies of Crohn's disease, from the linkage-based studies that first implicated the NOD2 locus, through to modern-day genome-wide association studies that have discovered over 140 loci associated with Crohn's disease and yielded novel insights into the biological pathways underlying pathogenesis. We describe on-going and future gene-mapping studies that utilise next generation sequencing technology to pinpoint causal variants and identify rare genetic variation underlying Crohn's disease risk. We comment on the utility of genetic markers for predicting an individual's disease risk and discuss their potential for identifying novel drug targets and influencing disease management. Finally, we describe how these studies have shaped and continue to shape our understanding of the genetic architecture of Crohn's disease.

Keywords: Crohn's; Genetics; Genomics; Genotyping; Sequencing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Crohn Disease / genetics*
  • Disease Susceptibility
  • Genetic Linkage
  • Genetic Markers
  • Genetic Predisposition to Disease*
  • Genetic Variation
  • Genome-Wide Association Study
  • Genomics
  • Humans
  • Nod2 Signaling Adaptor Protein / genetics
  • Risk Factors
  • Twin Studies as Topic


  • Genetic Markers
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein