title: Identification of major loci controlling clinical manifestations of ankylosing spondylitis.
abstract: OBJECTIVE
  To identify genomic regions linked with determinants of age at symptom onset, disease activity, and functional impairment in ankylosing spondylitis (AS).
  
  
  METHODS
  A whole genome linkage scan was performed in 188 affected sibling pair families with 454 affected individuals. Traits assessed were age at symptom onset, disease activity assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and functional impairment assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI). Parametric and nonparametric quantitative linkage analysis was performed using parameters defined in a previous segregation study.
  
  
  RESULTS
  Heritabilities of the traits studied in this data set were as follows: BASDAI 0.49 (P = 0.0001, 95% confidence interval [95% CI] 0.23-0.75), BASFI 0.76 (P = 10(-7), 95% CI 0.49-1.0), and age at symptom onset 0.33 (P = 0.005, 95% CI 0.04-0.62). No linkage was observed between the major histocompatibility complex (MHC) and any of the traits studied (logarithm of odds [LOD] score <1.0). "Significant" linkage (LOD score 4.0) was observed between a region on chromosome 18p and the BASDAI. Age at symptom onset showed "suggestive" linkage to chromosome 11p (LOD score 3.3). Maximum linkage with the BASFI was seen at chromosome 2q (LOD score 2.9).
  
  
  CONCLUSIONS
  In contrast to the genetic determinants of susceptibility to AS, clinical manifestations of the disease measured by the BASDAI, BASFI, and age at symptom onset are largely determined by a small number of genes not encoded within the MHC.
authors.affiliation: Musculoskeletal Sciences, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Headington OX3 7BN, UK. mbrown@well.ox.ac.uk
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Brown
authors.forename: Sinead
authors.initials: S
authors.lastname: Brophy
authors.forename: Linda
authors.initials: L
authors.lastname: Bradbury
authors.forename: Jasmin
authors.initials: J
authors.lastname: Hamersma
authors.forename: Andrew
authors.initials: A
authors.lastname: Timms
authors.forename: Steven
authors.initials: S
authors.lastname: Laval
authors.forename: Lon
authors.initials: L
authors.lastname: Cardon
authors.forename: Andrei
authors.initials: A
authors.lastname: Calin
authors.forename: B Paul
authors.initials: BP
authors.lastname: Wordsworth
mesh_terms: D002880:Chromosomes, Human, Pair 11; D002896:Chromosomes, Human, Pair 6; D005192:Family Health; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008126:Lod Score; D013167:Spondylitis, Ankylosing / Q000235:genetics*