Open Access Open Badges Research article

Linkage analysis of HLA and candidate genes for celiac disease in a North American family-based study

Susan L Neuhausen1*, Michael Feolo12, James Farnham1, Linda Book3 and John J Zone4

Author Affiliations

1 Medical Informatics, University of Utah, Salt Lake City, UT, USA

2 National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA

3 Pediatric Gastroenterology and Nutrition, Department Pediatrics, University of Utah, Salt Lake City, UT, USA

4 Dermatology, University of Utah, Salt Lake City, UT, USA

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BMC Medical Genetics 2001, 2:12  doi:10.1186/1471-2350-2-12

Published: 30 November 2001



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.


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.


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.


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.