Coeliac disease: follow-up linkage study provides further support for existence of a susceptibility locus on chromosome 11p11

Susceptibility to coeliac disease has a strong genetic component. The HLA a ssociations have been well described but, it is clear that, other genes out side this region must also be involved in disease development. Two previous genome-wide linkage studies using the affected sib pair method produced co nflicting results. Our own family based linkage study of 16 highly informat ive pedigrees identified 17 possibly linked regions, each of which produced a result significant at p < 0.05 or less. We have now investigated these 17 regions in a larger set of pedigrees usin g more finely spaced markers. Fifty multiply affected families were studied , comprising the 16 pedigrees from the original genome screen plus 34 new h ighly informative,e pedigrees. A total of 128 microsatellite markers were g enotyped with an average spacing between markers of 5 cM. Two-point and thr ee-point linkage analysis using classical and model free methods identified five potential susceptibility loci ,vith heterogeneity lod scores > 2.0, a t 6p12, 11p11, 17q12, 18q23 and 22q13.3. The most significant was a heterog eneity lod of 2.6 at D11S914 on chromosome 11p11. This marker maps to a pos ition implicated in one of the two previous genome scans and taken together these results provide strong support for the existence of a susceptibility locus in this region.