Linkage analysis of human systemic lupus erythematosus-related traits - A principal component approach

Objective. To identify chromosomal regions containing genes involved in the susceptibility to human systemic lupus erythematosus (SLE)-related traits. Methods. In the context of a genome scan, we analyzed 101 SLE-affected sibp airs with respect to dermatologic, renal, immunologic, hematologic, neurolo gic, cardiopulmonary, and arthritic characteristics. Phenotypes were redefi ned in terms of principal components, which are synthetic variables compose d of linear combinations of the original traits. Using 9 principal componen ts obtained from these 7 traits plus age at SLE onset and race, we analyzed genome scan data with the multivariate version of the new Haseman-Elston r egression model. Results. The largest linkage for an individual trait was on chromosome 2 at 228 cM (immunologic; P = 0.00048). The most significant linkage to an indi vidual principal component was on chromosome 4 at 208 cM (P = 0.00007). The largest multivariate linkage was on chromosome 7 at 69 cM (P = 0.0001). Of the individual organ systems, dermatologic involvement had the largest eff ect (P = 0.0083) at this peak at 7p13 on chromosome 7. Further analyses rev ealed that malar rash, a subtype of dermatologic involvement, was linked si gnificantly (P = 0.00458) to this location. Conclusion. These results provide evidence of the presence and locations of genes that are involved in the genetic susceptibility to SLE-related trait s in humans.