Evidence for a susceptibility gene, SLEV1, on chromosome 17p13 in familieswith vitiligo-related systemic lupus erythematosus

Both systemic lupus erythematosus (SLE) and vitiligo are autoimmune disorde rs that have strong evidence of complex genetic contributions to their etio logy, but, to date, efforts using genetic linkage to find the susceptibilit y genes for either phenotype have met with limited success. Since autoimmun e diseases are thought to share at least some of their genetic origins, and since only a small minority (16 of 92) of the European-American pedigrees multiplex for SLE in our collection have one or more affected members with vitiligo, we hypothesized that these pedigrees might be more genetically ho mogeneous at loci important to both SLE and vitiligo and, hence, have incre ased power for detection of linkage. We therefore evaluated genomewide micr osatellite-marker-scan data for markers at an average marker density of sim ilar to 11 cM in these 16 European-American pedigrees and identified a sign ificant linkage at 17p13, where the maximum multipoint parametric LOD score was 3.64 (P<4.3x10(-5)) and the nonparametric linkage score was 4.02 (P<2. 8x10(-5)), respectively. The segregation behavior of this linkage suggests a recessive mode of inheritance with a virtually homogeneous genetic effect in these 16 pedigrees. These results support the hypotheses that SLE and v itiligo may share important genetic effects and that sampling on the basis of clinical covariates dramatically improves power to identify genetic effe cts.