Genetics of coeliac disease.
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.
Houlston
R S
RS
Section of Epidemiology, Institute of Cancer Research, Sutton, UK.
Ford
D
D
D002446:Celiac Disease / Q000235:genetics*; D004198:Disease Susceptibility; D008040:Genetic Linkage; D006801:Humans; D008285:Major Histocompatibility Complex; D012307:Risk Factors