Celiac disease: Strongly heritable, oligogenic, but genetically complex

Celiac disease, or gluten-sensitive enteropathy, is a small intestinal disorder which affects up to 1:250 people in the United States. Disease development has a strong genetic component, with a sibling relative risk (lambda s) of 30. One susceptibility locus is the MHC region, with a particular association with the HLA-DQ alleles DQA1*0501 and DQB1*0201. However, haplotype sharing studies suggest that genes within the MHC complex contribute no more than 40% to the sibling familial risk of disease. This means that the stronger genetic risk is Likely to be conferred by a small number of non-HLA-linked genes. Genome-wide linkage studies, plus linkage and association studies of candidate loci have been used to try to identify these genes. However, these studies have either failed to detect loci, or produced inconsistent results. Such difficulties in identifying susceptibility genes are encountered when investigating any complex genetic disorder. Information from the Human Genome Project, coupled with new technology for high throughput single nucleotide polymorphism typing may help to identify the non-HLA determinants of celiac disease in the future. (C) 2000 Academic Press.