A combined genetics and genomics approach to unravelling molecular pathways in coeliac disease

Novartis Found Symp. 2005;267:113-34; discussion 134-44.


Coeliac disease (CD) is a complex, inflammatory disorder of the small intestine induced by gluten. It is common and has a prevalence of approximately 1:200 in Western populations. A major known susceptibility locus for CD is the HLA -DQ locus. However, the genetic contribution of this region is limited to approximately 40%, so non-HLA genes must also be involved in the disease aetiology. Genetic studies have so far identified multiple loci that may potentially be involved in disease aetiology, although the majority of these loci are expected to point to genes with a small effect. A major CD locus on chromosome 19 was recently identified in the Dutch population. Interestingly, there is some marked overlap when comparing genetic linkage studies conducted in different autoimmune disorders, suggesting that common pathways contribute to these diseases. This knowledge may eventually help in identifying some of the disease genes. To identify the true disease-causing genes, linkage analysis needs to be followed by genetic association. Because of the nature of the probable mutations, it is to be expected that the investigation of gene expression data can assist in selecting candidate genes from linkage regions. Furthermore, expression data will point to the molecular pathways involved in the disease pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Celiac Disease / genetics*
  • Genetic Linkage
  • Genetic Predisposition to Disease*
  • Genomics*
  • HLA-DQ Antigens / genetics
  • Humans


  • HLA-DQ Antigens