Genetic linkage and transmission disequilibrium of marker haplotypes at chromosome 1q41 in human systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characte rized by the production of autoantibodies to a wide range of self-antigens. Recent genome screens have implicated numerous chromosomal regions as pote ntial SLE susceptibility loci. Among these, the 1q41 locus is of particular interest, because evidence for linkage has been found in several independe nt SLE family collections. Additionally, the 1q41 locus appears to be synte nic with a susceptibility interval identified in the NZM2410 mouse model fo r SLE. Here, we report the results of genotyping of 11 microsatellite marke rs within the 1q41 region in 210 SLE sibpair and 122 SLE trio families. The se data confirm the modest evidence for linkage at 1q41 in our family colle ction (LOD = 1.21 at marker D1S2616). Evidence for significant linkage dise quilibrium in this interval was also found. Multiple markers in the region exhibit transmission disequilibrium, with the peak single marker multiallel ic linkage disequilibrium noted at D1S490 (pedigree disequilibrium test [PD T] global P value = 0.0091). Two- and three-marker haplotypes from the 1q41 region similarly showed strong transmission distortion in the collection o f 332 SLE families. The finding of linkage together with significant transm ission disequilibrium provides strong evidence for a susceptibility locus a t 1q41 in human SLE.