Genomewide linkage analysis of celiac disease in Finnish families

Celiac disease (CD), or gluten-sensitive enteropathy, is a common multifact orial disorder resulting from intolerance to cereal prolamins. The only est ablished genetic susceptibility factor is HLA-DQ, which appears to explain only part of the overall genetic risk. We performed a genomewide scan of CD in 60 Finnish families. In addition to strong evidence for linkage to the HLA region at 6p21.3 (Z(max)>5), suggestive evidence for linkage was found for six other chromosomal regions-1p36, 4p15, 5q31, 7q21, 9p21-23, and 16q1 2. We further analyzed the three most convincing regions-4p15, 5q31, and 7q 21- by evaluation of dense marker arrays across each region and by analysis of an additional 38 families. Although multipoint analysis with dense mark ers provided supportive evidence (multipoint LOD scores 3.25 at 4p15, 1.49 at 5q31, and 1.04 at 7q21) for the initial findings, the additional 38 fami lies did not strengthen evidence for linkage. The role that HLA-DQ plays wa s studied in more detail by analysis of DQB1 alleles in all 98 families. Al l but one patient carried one or two HLA-DQ risk alleles, and 65% of HLA-DQ 2 carriers were affected. Our study indicates that the HLA region harbors a predominant CD-susceptibility locus in these Finnish families.