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

Background Ankylosing spondylitis is a genetically determined and commonly familial disorder. Men and women differ in their susceptibility to ankylosi ng spondylitis, with about 2.5 men affected for every woman with the diseas e. We investigated the influence of the sex of the index case on disease pe netrance within families. Methods The ages at which 50% and 75% of patients were diagnosed with ankyl osing spondylitis were ascertained from a database of 4400 cases. Index pat ients with children or siblings who were old enough to have obtained a diag nosis (50% and 75% rates) were assessed for prevalence of disease among rel atives. 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 rat io 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 (less than or equal to 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 c hildren or siblings of female patients with ankylosing spondylitis. By cont rast, 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 siste rs (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 child ren. The striking maternal effect is greatest for women with young age at o nset, which is not seen in men. The sex ratio of affected children depends on the sex of the affected parent.