Identification of susceptibility loci in IL6, RPS9/LILRB3, and an intergenic locus on chromosome 21q22 in takayasu arteritis in a genome-wide association study

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dc.contributor.authorRenauer P.A.
dc.contributor.authorSaruhan-Direskeneli G.
dc.contributor.authorCoit P.
dc.contributor.authorAdler A.
dc.contributor.authorAksu K.
dc.contributor.authorKeser G.
dc.contributor.authorAlibaz-Oner F.
dc.contributor.authorAydin S.Z.
dc.contributor.authorKamali S.
dc.contributor.authorInanc M.
dc.contributor.authorCarette S.
dc.contributor.authorCuthbertson D.
dc.contributor.authorHoffman G.S.
dc.contributor.authorAkar S.
dc.contributor.authorOnen F.
dc.contributor.authorAkkoc N.
dc.contributor.authorKhalidi N.A.
dc.contributor.authorKoening C.
dc.contributor.authorKaradag O.
dc.contributor.authorKiraz S.
dc.contributor.authorLangford C.A.
dc.contributor.authorMaksimowicz-Mckinnon K.
dc.contributor.authorMcAlear C.A.
dc.contributor.authorOzbalkan Z.
dc.contributor.authorAtes A.
dc.contributor.authorKaraaslan Y.
dc.contributor.authorDuzgun N.
dc.contributor.authorMonach P.A.
dc.contributor.authorOzer H.T.E.
dc.contributor.authorErken E.
dc.contributor.authorOzturk M.A.
dc.contributor.authorYazici A.
dc.contributor.authorCefle A.
dc.contributor.authorOnat A.M.
dc.contributor.authorKisacik B.
dc.contributor.authorPagnoux C.
dc.contributor.authorKasifoglu T.
dc.contributor.authorSeyahi E.
dc.contributor.authorFresko I.
dc.contributor.authorSeo P.
dc.contributor.authorSreih A.G.
dc.contributor.authorWarrington K.J.
dc.contributor.authorYtterberg S.R.
dc.contributor.authorCobankara V.
dc.contributor.authorCunninghame-Graham D.S.
dc.contributor.authorVyse T.J.
dc.contributor.authorPamuk O.N.
dc.contributor.authorErcan Tunc S.
dc.contributor.authorDalkilic E.
dc.contributor.authorBicakcigil M.
dc.contributor.authorYentur S.P.
dc.contributor.authorWren J.D.
dc.contributor.authorMerkel P.A.
dc.contributor.authorDireskeneli H.
dc.contributor.authorSawalha A.H.
dc.date.accessioned2019-10-27T08:21:39Z
dc.date.available2019-10-27T08:21:39Z
dc.date.issued2015
dc.departmentEge Üniversitesien_US
dc.description.abstractObjective Takayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome-wide association analysis of Takayasu arteritis. Methods Two independent cohorts of patients with Takayasu arteritis from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 patients and 1,047 controls of European ancestry. Genotyping was performed using the Omni1-Quad and Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality control measures and subsequently analyzed to discover genetic susceptibility loci for Takayasu arteritis. Results We identified genetic susceptibility loci for Takayasu arteritis with a genome-wide level of significance in IL6 (rs2069837) (odds ratio [OR] 2.07, P = 6.70 × 10-9), RPS9/LILRB3 (rs11666543) (OR 1.65, P = 2.34 × 10-8), and an intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 × 10-10). The genetic susceptibility locus in RPS9/LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin-like receptor gene LILRB3 (P = 2.29 × 10-8). In addition, we identified candidate susceptibility genes with suggestive levels of association (P < 1 × 10-5) with Takayasu arteritis, including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B. Conclusion Our findings indicate novel genetic susceptibility loci for Takayasu arteritis and uncover potentially important aspects of the pathophysiology of this form of vasculitis. © 2015, American College of Rheumatology.en_US
dc.identifier.doi10.1002/art.39035en_US
dc.identifier.endpage1368en_US
dc.identifier.issn2326-5191
dc.identifier.issue5en_US
dc.identifier.pmid25604533en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage1361en_US
dc.identifier.urihttps://doi.org/10.1002/art.39035
dc.identifier.urihttps://hdl.handle.net/11454/26078
dc.identifier.volume67en_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherJohn Wiley and Sons Inc.en_US
dc.relation.ispartofArthritis and Rheumatologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.titleIdentification of susceptibility loci in IL6, RPS9/LILRB3, and an intergenic locus on chromosome 21q22 in takayasu arteritis in a genome-wide association studyen_US
dc.typeArticleen_US

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