Objective: To replicate and refine the reported association of ankylosing spondylitis (AS) with 2 non-synonymous single nucleotide polymorphisms (nsSNPs) on chromosome 16q22.1.
Methods: First, we genotyped 730 independent UK AS patients for rs9939768 and rs6979 and compared allele frequencies with 2879 previously typed historic disease controls. Second, we combined the 2 data sets in meta-analyses. Finally, we analysed 5 tagging SNPs located between rs9939768 and rs6979, in 1604 cases and 1020 controls.
Results: We replicated the association of rs6979 with AS, p = 0.03, odds ratio (OR) (95% confidence interval) = 1.14 (1.01-1.28), and detected a trend for association with rs9939768, p = 0.06, OR = 1.25 (0.99-1.57). Meta-analyses revealed association of both SNPs with AS, p = 0.0008, OR = 1.31 (1.12-1.54) and p = 0.0009, OR = 1.15 (1.06-1.23) for rs9939768 and rs6979, respectively. We identified new associations with rs9033 and rs868213 (p = 0.00002, OR = 1.23 (1.12-1.36) and p = 0.00002 OR = 1.45 (1.22-1.72), respectively.
Conclusions: The region on chromosome 16 that we have replicated is interesting as the highly plausible candidate gene, TRADD, is located between rs9033 and rs868213. It will require additional work to identify the primary genetic association(s) with AS.