An autosomal screen for genes that predispose to celiac disease in the western counties of Ireland
- 1 November 1996
- journal article
- research article
- Published by Springer Nature in Nature Genetics
- Vol. 14 (3) , 329-333
- https://doi.org/10.1038/ng1196-329
Abstract
Celiac disease is a strongly heritable gastrointestinal illness that is an especially important model of the genetically complex multifactorial immune-mediated diseases1. The HLA component of celiac disease (a specific HLA-DQ heterodimer)is largely established and is relatively uncomplicated2,3, and the environmental component (gluten and related grain storage proteins in the diet) is remarkably well understood4. Previous family studies of celiac disease5–8 suggested that there is at least one important non-HLA locus. This locus may be a stronger genetic factor than HLA7, and it apparently has a recessive mode of inheritance5,6,8. We used a three-step genome screening protocol to identify loci that contribute to celiac disease in the western counties of Ireland, a region with the highest prevalence of celiac disease in the world9. The most significant of several possible non-HLA loci that we found was on chromosome 6p about 30 cM telomeric from HLA. It has a multipoint maximum lod score of 4.66 (compared with 4.44 for HLA-DQ) and appears to have a recessive mode of inheritance. Our study localizes and provides strong evidence for linkage of at least one non-HLA locus to celiac disease and may serve as a prototype for an efficient approach to screening the human genome for loci that contribute to complex diseases.Keywords
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