2009 - 2010 Current Research
Finding more disease genes will require analysis of thousands more samples. We have formed a large collaborative group to enable this, and have been awarded (Feb 2008) a major collaborative grant by the Wellcome Trust charity. Our current collaborators are based in the UK, the Netherlands, Ireland, Finland (genome scan samples), Spain, US, Hungary, Italy, Sweden, Norway (replication samples).
We currently aim to:
- precisely localise from each region the disease causing genetic change ('fine-mapping'). The current markers we have identified for each region are probably just tagging (i.e. correlated with) the true causal variant.
- discover more coeliac disease predisposing genetic variants
- understand how the coeliac disease genetic variants are influencing biological function
2008 Genome Wide Association (GWA) Study Follow-up
To follow on from our first GWA study we followed up 1,020 of the top associated SNPs from the British GWA study in a further set of 1,643 patients with coeliac disease and 3,406 population control samples from Britain, The Netherlands and Ireland. This study was published in Nature Genetics in March 2008.
We identified seven further gene regions predisposing to coeliac disease. There are now nine coeliac gene regions identified, including the 2007 IL2-IL21 finding and the long-recognised HLA-DQ association. Of the nine regions, eight contain likely candidate genes involved in immune system function. This agrees nicely with what we know about the immunology of coeliac disease. We know how genetic variation influences biological function for HLA-DQ, and we reported possible mechanisms for two of the new findings: SH2B3 and IL18RAP.
Interestingly there seems to be substantial overlap of gene regions with other autoimmune diseases, particularly four of the nine coeliac regions also predispose to type 1 (early onset) diabetes. We have been awarded a grant from the Juvenile Diabetes Research Foundation to study potential common mechanisms of these diseases.
The Daily Telegraph newspaper published an article about this project.
2007 Genome Wide Association (GWA) Study
Professor David van Heel's group carried out the first ever coeliac disease genome wide association study, published in the journal Nature Genetics in June 2007. The primary study was performed on a British sample collection, with replication of the major finding in a Dutch and an Irish sample collection.
The aim of this study was to compare the DNA between a group of coeliac disease patients and a group of unaffected controls. The result was that people with coeliac disease were found to be more likely to have a specific group of genetic changes within immune control genes than the controls. This is only the first step, however, as these genetic changes only explain a very small amount of way coeliac disease runs in families.
The Guardian newspaper published an article about this project.
For this project, 310,605 genetic variants (single nucleotide polymorphisms, SNPS) were tested for association using genechip technology in samples from 778 coeliac disease individuals and 1,422 population controls (British 1958 Birth Cohort). Genetic variants in the IL2/IL21 gene region were identified as risk factors predisposing to coeliac disease.
All our research is performed on human samples (we do no animal based research). Our studies have all been approved by independent research ethics committees from the UK