Identifying rare large effect size genetic variants predisposing to coeliac disease
Principal investigator: Professor David van Heel
Institution: Blizard Institute of Cell and Molecular Science, Centre for Digestive Diseases and Barts and The London School of Medicine and Dentistry, Queen Mary University of London
Research classification: Aetiology
Project start & duration: 1 Feb 2010 (36 months)
Grant awarded: £143k
This study will substantially advance our understanding of the genetic causes of coeliac disease with longer term implications for diagnosis and treatment.
Coeliac disease partly runs in families and we know there is a strong inherited genetic tendency. The HLA-DQ genetic variation has been long recognised. In the last 2 years, 13 further regions containing inherited genetic variants have been identified, most of which seem to influence the immune system. Many are shared with other chronic immune disease, for example Type 1 diabetes.
Despite these advances the majority (approximately 60%) of the known heritability of coeliac disease remains unexplained. Part of this may be due to rare genetic ‘mutations’.
The protein coding regions of all genes (approximately 180,000 exons) will be DNA sequenced in 96 people with coeliac disease, using new genomic technologies. There will most probably be many variants and therefore this research will also aim to predict how likely any one variant is to be a true coeliac disease causing mutation, rather than just a chance finding.
Those variants identified to be most associated with coeliac disease will be assessed in a collection of 8,000 UK DNA samples taken from people with coeliac disease and 8,000 control samples collected from the general healthy population.