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Although, a handful of non-HLA risk loci have been identified, capturing the unexplained genetic contribution to AS pathogenesis remains a challenge attributed to additive, pleiotropic and epistatic-interactions at the molecular level. Here, we developed multiple integrated genomic approaches to quantify molecular convergence of non-HLA loci with global immune mediated diseases. We show that non-HLA genes are significantly sensitive to deleterious mutation accumulation in the general population compared with tolerant genes. Human developmental proteomics (prenatal to adult) analysis revealed that proteins encoded by non-HLA AS risk loci are 2-fold more expressed in adult hematopoietic cells.Enrichment analysis revealed AS risk genes overlap with a significant number of immune related pathways (<jats:italic>p<\/jats:italic>\u2009<jats:italic>&lt;<\/jats:italic>\u20090.0001 to 9.8\u2009\u00d7\u200910<jats:sup>-12<\/jats:sup>). Protein-protein interaction analysis revealed non-shared AS risk genes are highly clustered seeds that significantly converge (empirical; <jats:italic>p<\/jats:italic>\u2009<jats:italic>&lt;<\/jats:italic>\u20090.01 to 1.6\u2009\u00d7\u200910<jats:sup>-4<\/jats:sup>) into networks of global immune mediated disease risk loci. We have also provided initial evidence for the involvement of <jats:italic>STAT2<\/jats:italic>\/<jats:italic>3<\/jats:italic> in AS pathogenesis. Collectively, these findings highlight molecular insight on non-HLA AS risk loci that are not exclusively connected with overlapping immune mediated diseases; rather a component of common pathophysiological pathways with other immune mediated diseases. This information will be pivotal to fully explain AS pathogenesis and identify new therapeutic targets.<\/jats:p>","DOI":"10.1038\/srep10314","type":"journal-article","created":{"date-parts":[[2015,5,18]],"date-time":"2015-05-18T12:48:20Z","timestamp":1431953300000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Integrated Genomics Identifies Convergence of Ankylosing Spondylitis with Global Immune Mediated Disease Pathways"],"prefix":"10.1038","volume":"5","author":[{"given":"Mohammed","family":"Uddin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianne","family":"Codner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S M","family":"Mahmud Hasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen W","family":"Scherer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren D","family":"O\u2019Rielly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Proton","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,5,18]]},"reference":[{"key":"BFsrep10314_CR1","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1186\/ar4532","volume":"16","author":"AT Masi","year":"2014","unstructured":"Masi, A. 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