A genome-wide search for susceptibility genes in human systemic lupus erythematosus sib-pair families

Systemic lupus erythematosus (SLE) is an autoimmune multisystem inflammator y disease characterized by the production of pathogenic autoantibodies. Pre vious genetic studies have suggested associations with HLA Class II alleles , complement gene deficiencies, and Pc receptor polymorphisms; however, it is likely that other genes contribute to SLE susceptibility and pathogenesi s. Here, we report the results of a genome-wide microsatellite marker scree n in 105 SLE sib-pair families. By using multipoint nonparametric methods, the strongest evidence for linkage was found near the HLA locus (6p11-p21) [D6S257, logarithm of odds (lod) = 3.90, P = 0.000011] and at three additio nal regions: 16q13 (D16S415, lod = 3.64, P = 0.000022), 14q21-23 (D14S276, lod = 2.81, P = 0.00016), and 20p12 (D20S186, lod = 2.62, P = 0.00025). Ano ther nine regions (1p36, 1p13, 1q42, 2p15, 2q21-33, 3cent-q11, 4q28, 11p15, and 15q26) were identified with lod scores greater than or equal to 1.00. These data support the hypothesis that multiple genes, including one in the HLA region, influence susceptibility to human SLE.