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OBJECTIVE: Ankylosing spondylitis (AS) is a debilitating chronic inflammatory condition with a high degree of familiality (lambda(s) = 82) and heritability (>90%) that primarily affects spinal and sacroiliac joints. Whole genome scans for linkage to AS phenotypes have been conducted, although results have been inconsistent between studies and all have had modest sample sizes. One potential solution to these issues is to combine data from multiple studies in a retrospective meta-analysis. METHODS: The International Genetics of Ankylosing Spondylitis Consortium combined data from three whole genome linkage scans for AS (n = 3744 subjects) to determine chromosomal markers that show evidence of linkage with disease. Linkage markers typed in different centres were integrated into a consensus map to facilitate effective data pooling. We performed a weighted meta-analysis to combine the linkage results, and compared them with the three individual scans and a combined pooled scan. RESULTS: In addition to the expected region surrounding the HLA-B27 gene on chromosome 6, we determined that several marker regions showed significant evidence of linkage with disease status. Regions on chromosome 10q and 16q achieved 'suggestive' evidence of linkage, and regions on chromosomes 1q, 3q, 5q, 6q, 9q, 17q and 19q showed at least nominal linkage in two or more scans and in the weighted meta-analysis. Regions previously associated with AS on chromosome 2q (the IL-1 gene cluster) and 22q (CYP2D6) exhibited nominal linkage in the meta-analysis, providing further statistical support for their involvement in susceptibility to AS. CONCLUSION: These findings provide a useful guide for future studies aiming to identify the genes involved in this highly heritable condition.

Original publication

DOI

10.1093/rheumatology/kel443

Type

Journal article

Journal

Rheumatology (Oxford, England)

Publication Date

05/2007

Volume

46

Pages

763 - 771

Addresses

Laboratory for Genetic Epidemiology, Western Australian Institute for Medical Research, UWA Centre for Medical Research, University of Western Australia, Nedlands, Western Australia 6009, Australia. kcarter@cyllene.uwa.edu.au.

Keywords

Chromosomes, Human, Pair 2, Chromosomes, Human, Pair 22, Humans, Spondylitis, Ankylosing, Genetic Predisposition to Disease, Retrospective Studies, Genome, Human, Female, Male, Genetic Linkage