UMCG staff Cisca Wijmenga, Gosia Trynka, Eleanora Festen, and Rinse Weersma have worked on a new paper published in PloS Genetics (Jan 2011).
An investigation has found that celiac disease and Crohn’s disease, both inflammatory diseases of the gastrointestinal tract, share at least four genetic risk loci. Together, researchers from the University of Groningen, The Netherlands; the Broad Institute, USA; the Université de Montréal and Montreal Heart Institute in Canada performed a combined meta-analysis of genome-wide data for celiac disease and Crohn’s disease. This meta-analysis, published in the open-access journal PLoS Genetics on January 27, has identified two new shared risk loci and two shared risk loci that had previously been independently identified for each disease.
The pathogenesis of both celiac disease and Crohn’s disease is only partly understood, although it is known that they are affected by both genetic and environmental risk factors. At least one in every hundred individuals in the Western world develop celiac disease; Crohn’s disease is much less common but can be accompanied by more severe symptoms as it can affect the whole gastrointestinal tract. Celiac patients develop an inflammation of the small bowel in reaction to gluten, whereas there is no specific known autoantigen for Crohn’s disease. However, the primary cause of Crohn’s disease is thought to be a dysregulated immune response to gut bacteria. In order to gain a better understanding of the pathogenesis and to aid in developing therapies against these disorders, knowledge of the genetic background of the diseases is vital.
As it has previously been shown that celiac patients are at a higher risk of developing Crohn’s disease than non-sufferers, it had been thought that the two illnesses would share genetic risk loci.
This study combined the results from the genetic investigations into both diseases to show that part of the genetic background of Crohn’s disease and celiac disease is shared, which confirms a common pathogenesis for these disorders. Although additional studies will be necessary to understand the mechanisms by which these variants influence both Crohn’s disease and celiac, the current study provides a proof-of-principle that risk factors shared across related diseases can be identified by directly combining genetic data from clinically distinct diseases.
Link to full paper here (open access)
See also Science Daily (latest research news) here
The study was supported by the Celiac Disease Consortium, an Innovative Cluster approved by the Netherlands Genomics Initiative and partially funded by the Dutch Government (BSIK03009); by the Netherlands Organization for Scientific Research (NWO, VICI grant 918.66.620 to CW [one of the authors], AGIKO grant 92.003.533 to EAMF [author], KF grant 907.00.281 to RKW [author]); by the Wellcome Trust (grant WT084743MA to DAvH [author]); by the National Institutes of Allergy and Infectious Diseases (grant AI065687, AI067152 to JDR [author]); by the National Institute of Diabetes and Digestive and Kidney Diseases (grant DK064869, DK062432 to JDR); and by the Crohn’s and Colitis Foundation of America (grant SRA512 to JDR). EAMF is a MD-medical research trainee with financial support from The Netherlands Organisation for Health Research and Development. GT [author] was awarded a Ter Meulen Fund travel grant by the Royal Netherlands Academy of Arts and Sciences (KNAW). PCD [author] is a MRC Clinical Training Fellow (G0700545). The British 1958 Birth Cohort collection was funded by the UK Medical Research Council (grant G0000934) and the Wellcome Trust (grant 068545/Z/02). Funding for the project Wellcome Trust Case-Control Consortium 2 data was provided by the Wellcome Trust under award 085475. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
The authors have declared that no competing interests exist.
Festen EAM, Goyette P, Green T, Boucher G, Beauchamp C, et al. (2011) A Meta-Analysis of Genome-Wide Association Scans Identifies IL18RAP, PTPN2,
TAGAP, and PUS10 As Shared Risk Loci for Crohn’s Disease and Celiac Disease. PLoS Genet 7(1): e1001283. doi:10.1371/journal.pgen.1001283
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