title: Linkage analysis of human systemic lupus erythematosus-related traits: a principal component approach.
abstract: 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 sibpairs with respect to dermatologic, renal, immunologic, hematologic, neurologic, cardiopulmonary, and arthritic characteristics. Phenotypes were redefined in terms of principal components, which are synthetic variables composed of linear combinations of the original traits. Using 9 principal components 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 regression 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 individual 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 effect (P = 0.0083) at this peak at 7p13 on chromosome 7. Further analyses revealed that malar rash, a subtype of dermatologic involvement, was linked significantly (P = 0.00458) to this location.
  
  
  CONCLUSIONS
  These results provide evidence of the presence and locations of genes that are involved in the genetic susceptibility to SLE-related traits in humans.
authors.affiliation: Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: S
authors.initials: S
authors.lastname: Rao
authors.forename: J M
authors.initials: JM
authors.lastname: Olson
authors.forename: K L
authors.initials: KL
authors.lastname: Moser
authors.forename: C
authors.initials: C
authors.lastname: Gray-McGuire
authors.forename: G R
authors.initials: GR
authors.lastname: Bruner
authors.forename: J
authors.initials: J
authors.lastname: Kelly
authors.forename: J B
authors.initials: JB
authors.lastname: Harley
mesh_terms: D000328:Adult; D002889:Chromosomes, Human, Pair 2; D002894:Chromosomes, Human, Pair 4; D002897:Chromosomes, Human, Pair 7; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D015999:Multivariate Analysis; D010641:Phenotype; D012044:Regression Analysis