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The IL23R region on chromosome 1 exhibits complex associations with ankylosing spondylitis (AS). We used publicly available epigenomic information and historical genetic association data to identify a putative regulatory element (PRE) in the intergenic region between IL23R and IL12RB2, which includes two single-nucleotide polymorphisms (SNPs) independently associated with AS-rs924080 (P=2 × 10 -3 ) and rs11578380 (P=2 × 10 -4 ). In luciferase reporter assays, this PRE showed silencer activity (P&lt;0.001). Haplotype and conditional analysis of 4230 historical AS cases and 9700 controls revealed a possible AS-associated extended haplotype, including the PRE and risk variants at three SNPs (rs11209026, rs11209032 and rs924080), but excluding the rs11578380 risk variant. However, the rs924080 association was absent after conditioning on the primary association with rs11209032, which, in contrast, was robust to conditioning on all other AS-associated SNPs in this region (P&lt;2 × 10 -8 ). The role of this putative silencer on some IL23R extended haplotypes therefore remains unclear.

Investigation of a possible extended risk haplotype in the IL23R region associated with ankylosing spondylitis