Recent genome-wide association studies (GWAS) for Ankylosing Spondylitis (AS) reported a strong association of rs2836883 SNP in an intergenic region of chromosome 21q22 with susceptibility to AS. This susceptibility locus has also been associated with GWAS of IBD and Takayasu’s Arteritis. We have preliminary data showing a long non-coding RNA (lnRNA) transcript encompassing the rs2836883 SNP, is highly expressed in primary monocytes of AS patients compared to healthy controls. We further demonstrate ETS2, a nearby gene of 21q22 lncRNAs, is highly correlated with increased 21q22 lncRNAs by correlation and eQTL studies. However, the functional roles of 21q22 lncRNAs and ETS2, and their biological mechanism in AS pathogenesis remain unknown. Here, we propose some functional assays in monocytes to study the relationship of 21q22 lncRNAs and ETS2, including siRNA knockdown, Chromatin and RNA immunoprecipitation (ChIP and RIP). We hope that these experiments will eventually provide new insight in understanding the pathogenesis of genetic variants for AS susceptibility.