1. Linkage analysis of HLA and candidate genes for celiac disease in a North American family-based study
- Author
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Susan L. Neuhausen, Linda S. Book, John J. Zone, Michael Feolo, and James M. Farnham
- Subjects
Candidate gene ,lcsh:Internal medicine ,lcsh:QH426-470 ,Disease ,Human leukocyte antigen ,Biology ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Genetic linkage ,Dermatitis herpetiformis ,medicine ,Genetics ,Genetics(clinical) ,lcsh:RC31-1245 ,Genetics (clinical) ,Genetic association ,nutritional and metabolic diseases ,medicine.disease ,digestive system diseases ,Human genetics ,3. Good health ,lcsh:Genetics ,030211 gastroenterology & hepatology ,030215 immunology ,Research Article - Abstract
Background Celiac disease has a strong genetic association with HLA. However, this association only explains approximately half of the sibling risk for celiac disease. Therefore, other genes must be involved in susceptibility to celiac disease. We tested for linkage to genes or loci that could play a role in pathogenesis of celiac disease. Methods DNA samples, from members of 62 families with a minimum of two cases of celiac disease, were genotyped at HLA and at 13 candidate gene regions, including CD4, CTLA4, four T-cell receptor regions, and 7 insulin-dependent diabetes regions. Two-point and multipoint heterogeneity LOD (HLOD) scores were examined. Results The highest two-point and multipoint HLOD scores were obtained in the HLA region, with a two-point HLOD of 3.1 and a multipoint HLOD of 5.0. For the candidate genes, we found no evidence for linkage. Conclusions Our significant evidence of linkage to HLA replicates the known linkage and association of HLA with CD. In our families, likely candidate genes did not explain the susceptibility to celiac disease.
- Published
- 2001