Identification of major loci controlling clinical manifestations of ankylosing spondylitis

Brown, Matthew A., Brophy, S., Bradbury, L., Hamersma, J., Timms, A., Laval, S., Cardon, L., Calin, A., & Wordsworth, B. P. (2003) Identification of major loci controlling clinical manifestations of ankylosing spondylitis. Arthritis and Rheumatism, 48(8), pp. 2234-2239.

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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.

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ID Code: 87766
Item Type: Journal Article
Refereed: Yes
Additional Information: No file attached.
Keywords: ankylosing spondylitis, article, bath ankylosing spondylitis disease activity index, Bath Ankylosing Spondylitis Functional Index, chromosome 11p, chromosome 18p, chromosome 2q, clinical feature, disease activity, family study, functional assessment, gene locus, genetic linkage, heritability, HLA system, human, major clinical study, major histocompatibility complex, onset age, priority journal, sibling, spondyloarthropathy, symptomatology, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 6, Family Health, Genetic Predisposition to Disease, Genome, Human, Genotype, Humans, Lod Score, Spondylitis, Ankylosing
DOI: 10.1002/art.11106
ISSN: 0004-3591
Divisions: Current > Schools > School of Biomedical Sciences
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 28 Sep 2015 06:26
Last Modified: 28 Sep 2015 06:26

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