Identification of major loci controlling clinical manifestations of ankylosing spondylitis
Article first published online: 1 AUG 2003
Copyright © 2003 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 48, Issue 8, pages 2234–2239, August 2003
How to Cite
Brown, M. A., Brophy, S., Bradbury, L., Hamersma, J., Timms, A., Laval, S., Cardon, L., Calin, A. and Wordsworth, B. P. (2003), Identification of major loci controlling clinical manifestations of ankylosing spondylitis. Arthritis & Rheumatism, 48: 2234–2239. doi: 10.1002/art.11106
- Issue published online: 1 AUG 2003
- Article first published online: 1 AUG 2003
- Manuscript Accepted: 14 APR 2003
- Manuscript Received: 25 FEB 2003
- Arthritis Research Campaign (UK)
- Oliver Bird Fund of the Nuffield Foundation
- Coates Foundation Trust
- Col. W. W. Pilkington Charitable Trust
To identify genomic regions linked with determinants of age at symptom onset, disease activity, and functional impairment in ankylosing spondylitis (AS).
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.
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).
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.