2 Genetics in coeliac disease David A. van Heel* DR Karen Hunt Department of Gastroenterology, Imperial College London, Du Cane Road, London W12 0NN, UK Luigi Greco DR Department of Paediatrics and International Laboratory for Food Induced Diseases, University of Naples Federico II, Naples, Italy Cisca Wijmenga Professor Complex Genetics Section, DBG-Dept. Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands Coeliac disease has a strong genetic component, higher than for many other common complex diseases. Possession of the HLA-DQ2 variant is required for presentation of disease causing dietary antigens to T cells, although this is also common in the healthy population. Non-HLA genetic factors account for the majority of heritable risk. Linkage studies have identified promising regions on chromosomes 5 and 19, with multiple other loci awaiting definitive confirmation in independent studies. Inherited variants in the tightly clustered chromosome 2q CD28-CTLA4-ICOS region are associated with disease, although of weak effect size. Larger sample sizes are necessary in coeliac disease genetic studies to detect small effects, alternatively meta-analysis offers promise. Newer methods including gene expression analysis and genome wide association studies will advance understanding of genetic susceptibility. Identification of coeliac disease genes may improve diagnostic/prognostic markers, basic understanding of disease aetiology, permit development of novel therapeutics and provide insight into other autoimmune disorders. Key words: coeliac; genetic; linkage; genome scan; association; CTLA4; Celiac. Coeliac disease is a chronic inflammatory disease of the small intestine induced by dietary proteins in wheat, rye and barley. Advances in understanding of disease immunology have identified immuno-dominant dietary (wheat gliadin) peptides resistant to intestinal enzymatic breakdown, modification of peptides by tissue transglutaminase (to which an antibody response is also made), and presentation of 1521-6918/$ - see front matter Q 2005 Elsevier Ltd. All rights reserved. Best Practice & Research Clinical Gastroenterology Vol. 19, No. 3, pp. 323–339, 2005 doi:10.1016/j.bpg.2005.01.001 available online at http://www.sciencedirect.com *Corresponding author. Tel.: C44 208 383 8067; Fax: C44 208 749 3436. E-mail address: d.vanheel@imperial.ac.uk (D.A. van Heel).