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Genetics of coeliac disease

R.S. Houlston, D. Ford
DOI: http://dx.doi.org/10.1093/qjmed/89.10.737 737-744 First published online: 1 October 1996


Coeliac disease is one of the most common gastrointestinal disorders. The clinical features of the disease are protean, possibly due to heterogeneity. A familial basis for coeliac disease is well recognized, and although a strong HLA association is seen, this cannot entirely account for the increased risk seen in relatives of affected cases. A gene (or genes) at an HLA-unlinked locus also participates in causing coeliac disease and is likely to be a stronger determinant of disease susceptibility than the HLA locus. Such a gene (or genes) could theoretically act either additively or multiplicatively in conjunction with HLA. However, the familial risks seen in siblings and monozygotic twins are most parsimonious with a multiplicative model. Without evidence for a particular HLA-unlinked gene, and because no genetic model can be reliably ascribed to the non-HLA linked locus, identifying causative non-linked HLA genes is likely to be through a genome-wide linkage search using non-parametric methods.