Impact of sex on inheritance of ankylosing spondylitis: a cohort study

Lancet. 1999 Nov 13;354(9191):1687-90. doi: 10.1016/S0140-6736(99)03219-5.


Background: Ankylosing spondylitis is a genetically determined and commonly familial disorder. Men and women differ in their susceptibility to ankylosing spondylitis, with about 2.5 men affected for every woman with the disease. We investigated the influence of the sex of the index case on disease penetrance within families.

Methods: The ages at which 50% and 75% of patients were diagnosed with ankylosing spondylitis were ascertained from a database of 4400 cases. Index patients with children or siblings who were old enough to have obtained a diagnosis (50% and 75% rates) were assessed for prevalence of disease among relatives. Confirmation of diagnosis for affected relatives was sought for all offspring and a random 25% selection of siblings.

Findings: Ankylosing spondylitis was more prevalent among children (odds ratio 1.9 [95% CI 1.2-3.0], p<0.005) and siblings (1.5 [1.2-1.9], p<0.0001) of female index cases than among those of male cases. Analyses restricted to index cases with a young age at onset (< or = 21 years) indicated that children of women had an even higher incidence of ankylosing spondylitis (7.2 [1.5-34], p=0.013) than did children of men at similar age at onset. 38% of children of female cases had disease compared with 8% of male cases. There was no difference in sex distribution among affected children or siblings of female patients with ankylosing spondylitis. By contrast, the sons and brothers of male patients had a higher prevalence of the disease (odds ratio 2.6 [1.4-5.2], p=0.003) than did daughters and sisters (1.7 [1.3-2.2], p<0.0001).

Interpretation: The influence of female sex is greater than that of male sex in determining increased susceptibility to ankylosing spondylitis in children. The striking maternal effect is greatest for women with young age at onset, which is not seen in men. The sex ratio of affected children depends on the sex of the affected parent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease / genetics*
  • HLA Antigens / genetics
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Risk Factors
  • Sex Ratio*
  • Spondylitis, Ankylosing / diagnosis
  • Spondylitis, Ankylosing / genetics*


  • HLA Antigens