Is disease severity in ankylosing spondylitis genetically determined?

Hamersma, J., Cardon, L. R., Bradbury, L., Brophy, S., Van Der Horst-Bruinsma, I., Calin, A., & Brown, M. A. (2001) Is disease severity in ankylosing spondylitis genetically determined? Arthritis and Rheumatism, 44(6), pp. 1396-1400.

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To assess the role of genes and the environment in determining the severity of ankylosing spondylitis.


One hundred seventy-three families with >1 case of ankylosing spondylitis were recruited (120 affected sibling pairs, 26 affected parent-child pairs, 20 families with both first- and second-degree relatives affected, and 7 families with only second-degree relatives affected), comprising a total of 384 affected individuals. Disease severity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and functional impairment was determined using the Bath Ankylosing Spondylitis Functional Index (BASFI). Disease duration and age at onset were also studied. Variance-components modeling was used to determine the genetic and environmental components Contributing to familiality of the traits examined, and complex segregation analysis was performed to assess different disease models.


Both the disease activity and functional capacity as assessed by the BASDAI and the BASFI, respectively, were found to be highly familial (BASDAI familiality 0.51 [P = 10-4], BASFI familiality 0,68 [P = 3 × 10-7]). No significant shared environmental component was demonstrated to be associated with either the BASDAI or the BASFI. Including age at disease onset and duration of disease as covariates made no difference in the heritability assessments. A strong correlation was noted between the BASDAI and the BASFI (genetic correlation 0.9), suggesting the presence of shared determinants of these 2 measures. However, there was significant residual heritability for each measure independent of the other (BASFI residual heritability 0.48, BASDAI 0,36), perhaps indicating that not all genes influencing disease activity influence chronicity. No significant heritability of age at disease onset was found (heritability 0.18; P = 0.2). Segregation studies suggested the presence of a single major gene influencing the BASDAI and the BASFI.


This study demonstrates a major genetic contribution to disease severity in ankylosing spondylitis. As with susceptibility to ankylosing spondylitis, shared environmental factors play little role in determining the disease severity.

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ID Code: 87776
Item Type: Journal Article
Refereed: Yes
Additional Information: No file attached.
Keywords: adolescent, adult, age, ankylosing spondylitis, article, child, disease activity, disease duration, disease severity, environmental factor, familial disease, female, genetic analysis, genetic predisposition, heredity, human, major clinical study, male, onset age, priority journal, Age of Onset, Aged, Aged, 80 and over, DNA, Family, Family Health, Genetic Predisposition to Disease, HLA-B Antigens, Humans, Middle Aged, Models, Genetic, Polymerase Chain Reaction, Questionnaires, Severity of Illness Index, Spondylitis, Ankylosing
DOI: 10.1002/1529-0131(200106)44:6<1396::AID-ART233>3.0.CO;2-A
ISSN: 0004-3591
Divisions: Current > Schools > School of Biomedical Sciences
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 28 Sep 2015 04:38
Last Modified: 28 Sep 2015 04:38

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