Ortiz-Fernández L.Saruhan-Direskeneli G.Alibaz-Oner F.Kaymaz-Tahra S.Coit P.Kong X.Kiprianos A.P.Maughan R.T.Aydin S.Z.Aksu K.Keser G.Kamali S.Inanc M.Springer J.Akar S.Onen F.Akkoc N.Khalidi N.A.Koening C.Karadag O.Kiraz S.Forbess L.Langford C.A.McAlear C.A.Ozbalkan Z.Yavuz S.Çetin G.Y.Alpay-Kanitez N.Chung S.Ates A.Karaaslan Y.McKinnon-Maksimowicz K.Monach P.A.Ozer H.T.E.Seyahi E.Fresko I.Cefle A.Seo P.Warrington K.J.Ozturk M.A.Ytterberg S.R.Cobankara V.Onat A.M.Duzgun N.Bıcakcıgil M.Yentür S.P.Lally L.Manfredi A.A.Baldissera E.Erken E.Yazici A.Kısacık B.Kaşifoğlu T.Dalkilic E.Cuthbertson D.Pagnoux C.Sreih A.Reales G.Wallace C.Wren J.D.Cunninghame-Graham D.S.Vyse T.J.Sun Y.Chen H.Grayson P.C.Tombetti E.Jiang L.Mason J.C.Merkel P.A.Direskeneli H.Sawalha A.H.2024-07-222024-07-22202100029297http://akademikarsiv.cbu.edu.tr:4000/handle/123456789/13502Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 × 10−5) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets. © 2020 American Society of Human GeneticsEnglishAll Open Access; Bronze Open AccessCase-Control StudiesFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInflammatory Bowel DiseasesMalePolymorphism, Single NucleotideTakayasu Arteritisfocal adhesion kinase 1interleukin 12p40aortic arch syndromeArticleB lymphocyteCFL2 genechromosome 13qchromosome 21qcohort analysiscontrolled studyepigeneticsETS2 genegenegene mappinggenetic predispositiongenetic risk scoregenome-wide association studyHLA systemhumanIL12B geneinflammatory bowel diseasemajor clinical studymonocytepathophysiologypriority journalPTK2B generisk factorsusceptibility locusSVEP1 geneVPS8 geneaortic arch syndromecase control studyfemalegeneticsgenome-wide association studymalemeta analysisproceduressingle nucleotide polymorphismArticle10.1016/j.ajhg.2020.11.014