title: The X-chromosome and susceptibility to ankylosing spondylitis.
abstract: OBJECTIVE
  Ankylosing spondylitis (AS) affects 0.25-1.0% of the population, and its etiology is incompletely understood. Susceptibility to this highly familial disease (lambda(s) = 58) is primarily genetically determined. There is a significant sex bias in AS, and there are differences in recurrence risk to the offspring of affected mothers and fathers, suggesting that there may be an X-linked recessive effect. We undertook an X-chromosome linkage study to determine any contribution of the X-chromosome to AS susceptibility.
  
  
  METHODS
  A linkage study of the X-chromosome using 234 affected sibling pairs was performed to investigate this hypothesis.
  
  
  RESULTS
  No linkage of the X-chromosome with susceptibility to AS was found. Model-free multipoint linkage analysis strongly excluded any significant genetic contribution (lambda > or = 1.5) to AS susceptibility encoded on the X-chromosome (logarithm of odds [LOD] <-2.0). Smaller genetic effects (lambda > or = 1.3) were also found to be unlikely (LOD <-1.0).
  
  
  CONCLUSIONS
  The sex bias in AS is not explained by X-chromosome-encoded genetic effects. The disease model best explaining the sex bias in occurrence and transmission of AS is a polygenic model with a higher susceptibility threshold in females.
authors.affiliation: Wellcome Trust Centre for Human Genetics, Headington, UK.
authors.forename: E
authors.initials: E
authors.lastname: Hoyle
authors.forename: S H
authors.initials: SH
authors.lastname: Laval
authors.forename: A
authors.initials: A
authors.lastname: Calin
authors.forename: B P
authors.initials: BP
authors.lastname: Wordsworth
authors.forename: M A
authors.initials: MA
authors.lastname: Brown
mesh_terms: D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008126:Lod Score; D013167:Spondylitis, Ankylosing / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics*