A genome-wide family-based linkage study of coeliac disease

The susceptibility to develop coeliac disease (CD) has a strong genetic component, which is not entirely explained, by HLA associations. Two previous genome wide linkage studies have been performed to identify additional loci outside this region. These studies both used a sib-pair design and produced conflicting results. Our aim is to identify non-MHC genetic loci contributing to coeliac disease using a family based linkage study. We performed a genome wide search in 16 highly informative multiply affected pedigrees using 400 microsatellite markers with an average spacing of 10 cM. Linkage analysis was performed using lod score and model free methods. We identified two new potential susceptibility loci with loci scores of 1.9, at 10q23.1, and 16q23.3. Significant, but lower lod scores were found for 6q14 (1.2), 11p11 (1.5), and 19q13.4 (0.9); areas implicated in a previous genome wide study. Lod scores of 0.9 were obtained for both D7S507, which lies 1 cM from the gammaT-cell receptor gene, and for D2S364, which lies 12 cM from the CTLA4 gene.