Confirmation of genetic linkage between human systemic lupus erythematosusand chromosome 1q41

Objective. Genetic susceptibility to systemic lupus erythematosus (SLE) is undoubtedly complex and, presumably, involves multiple loci. Linkage of SLE to D1S229 at chromosome 1q41 has been previously reported in a cohort of 5 2 affected sibpairs. The present study sought to confirm this reported link age in an independent cohort of 127 extended multiplex SLE pedigrees contai ning 107 affected sibpairs. Methods. Genotype data were collected for D1S229 and 18 flanking microsatel lite markers spanning chromosome 1q32-1q42. Analyses of genotype data inclu ded a model-based logarithm of odds (LOD) score approach, affected sibpair analyses, and transmission disequilibrium tests. Results. A maximum LOD score of 1.46 was found with D1S229 in a subgroup of 78 European American pedigrees, with additional support from multiple mark ers clustered around D1S229. Increased allele sharing in affected siblings was most significant at D1S2616, particularly in European Americans (P = 0. 0005), followed by D1S229 (P = 0.002), D1S490 (P = 0.028), and D1S1605 (P = 0.037). Although linkage in a subgroup of 40 African American pedigrees wa s not suggested by the analyses of any marker tested in the chromosomal reg ion surrounding D1S229, a maximum LOD score of 3.03 was found with D1S3462, mapped 15 centimorgans distal to D1S229. Conclusion. Our linkage analysis results in European Americans at D1S229 ar e remarkably similar to those previously reported. That at least 1 genetic effect near this locus is important for susceptibility to lupus should now be generally accepted, and efforts to identify the gene are thereby justifi ed.