Suggestive evidence for association of human chromosome 18q12-q21 and its orthologue on rat and mouse chromosome 18 with several autoimmune diseases

Some immune system disorders, such as type 1 diabetes, multiple sclerosis ( MS), and rheumatoid arthritis (RA), share common features: the presence of autoantibodies and self-reactive T-cells, and a genetic association with th e major histocompatibility complex. We have previously published evidence, from 1,708 families, for linkage and association of a haplotype of three ma rkers in the D18S487 region of chromosome 18q21 with type 1 diabetes. Here, the three markers were typed in an independent set of 627 families and, al though there was evidence for Linkage (maximum logarithm of odds score [MLS ] = 1.2; P = 0.02), no association was detected. Further linkage analysis r evealed suggestive evidence for linkage of chromosome 18q21 to type 1 diabe tes in 882 multiplex families (MLS = 2.2; lambdas = 1.2; P = 0.001), and by meta-analysis the orthologous region (also on chromosome 18) is linked to diabetes in rodents (P = 9 x 10(-4)). By meta-analysis, both human chromoso me 18q12-q21 and the rodent orthologous region show positive evidence for l inkage to an autoimmune phenotype (P = 0.004 and 2 x 10(-8), respectively, empirical P = 0.01 and 2 x 10(-4), respectively). In the diabetes-linked re gion of chromosome 18q12-q21, a candidate gene, deleted in colorectal carci noma (DCC), was tested for association with human autoimmunity in 3,380 fam ilies with type 1 diabetes, MS, and RA. A haplotype ("2-10") of two newly c haracterized microsatellite markers within DCC showed evidence for associat ion with autoimmunity (P = 5 x 10(-6)). Collectively, these data suggest th at a locus (or loci) exists on human chromosome 18q12-q21 that influences m ultiple autoimmune diseases and that this association might be conserved be tween species.