Extended genome wide association study in coeliac disease (360G-Wellcome-084743_Z_08_A)

£130,855

Coeliac disease is a common condition of children and adults, where dietary wheat rye and barley causes intestinal damage. Why only some of the population develop coeliac disease when nearly all eat wheat remains unclear, despite advances in understanding which wheat fragments presented by HLA-DQ2/8 generate T-cell mediated immune responses. HLADQ2/8 is common (30%) in the population, being necessary but not sufficient for disease. Coeliac disease has a strong inherited genetic tendency of which only a minor part is currently understood. We performed a genome wide association study in 778 coeliac cases and 1422 healthy controls using 310,605 Illumina SNP markers. A clear association was identified (which we have now replicated in five independent collections) in the IL2/IL21 gene cluster (van Heel et al. Nature Genetics 2007). Interestingly this region also contains risk variants for type 1 diabetes and rheumatoid arthritis. Current studies, using ~2000 cases and 3000 controls (WTCCC Nature 2007), have shown substantial gains in statistical power and identification of multiple disease risk variants. We therefore propose to both enlarge both sample size (to 6x the original coeliac study) and genomic coverage to include copy number variants, in order to identify further disease risk variants.

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Grant Details

Amount Awarded 130855
Applicant Surname van Heel
Approval Committee Genome-Wide Association Studies in Common Disease Committee 2008
Award Date 2009-06-08T00:00:00+00:00
Financial Year 2008/09
Grant Programme: Title Programme Grant
Internal ID 084743/Z/08/A
Lead Applicant Prof David van Heel
Other Applicant(s) Dr Ross Mcmanus, Prof Cisca Wijmenga, Prof Panagiotis Deloukas
Partnership Value 130855
Planned Dates: End Date 2011-04-30T00:00:00+00:00
Planned Dates: Start Date 2008-05-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London