Li Z.Wu X.Leo P.J.De Guzman E.Akkoc N.Breban M.MacFarlane G.J.Mahmoudi M.Marzo-Ortega H.Anderson L.K.Wheeler L.Chou C.-T.Harrison A.A.Stebbings S.Jones G.T.Bang S.-Y.Wang G.Jamshidi A.Farhadi E.Song J.Lin L.Li M.Wei J.C.-C.Martin N.G.Wright M.J.Lee M.Wang Y.Zhan J.Zhang J.-S.Wang X.Jin Z.-B.Weisman M.H.Gensler L.S.Ward M.M.Rahbar M.H.Diekman L.Kim T.-H.Reveille J.D.Wordsworth B.P.Xu H.Brown M.A.2024-07-222024-07-22202100034967http://akademikarsiv.cbu.edu.tr:4000/handle/123456789/13188Objective We sought to test the hypothesis that Polygenic Risk Scores (PRSs) have strong capacity to discriminate cases of ankylosing spondylitis (AS) from healthy controls and individuals in the community with chronic back pain. Methods PRSs were developed and validated in individuals of European and East Asian ethnicity, using data from genome-wide association studies in 15 585 AS cases and 20 452 controls. The discriminatory values of PRSs in these populations were compared with other widely used diagnostic tests, including C-reactive protein (CRP), HLA-B27 and sacroiliac MRI. Results In people of European descent, PRS had high discriminatory capacity with area under the curve (AUC) in receiver operator characteristic analysis of 0.924. This was significantly better than for HLA-B27 testing alone (AUC=0.869), MRI (AUC=0.885) or C-reactive protein (AUC=0.700). PRS developed and validated in individuals of East Asian descent performed similarly (AUC=0.948). Assuming a prior probability of AS of 10% such as in patients with chronic back pain under 45 years of age, compared with HLA-B27 testing alone, PRS provides higher positive values for 35% of patients and negative predictive values for 67.5% of patients. For PRS, in people of European descent, the maximum positive predictive value was 78.2% and negative predictive value was 100%, whereas for HLA-B27, these values were 51.9% and 97.9%, respectively. Conclusions PRS have higher discriminatory capacity for AS than CRP, sacroiliac MRI or HLA-B27 status alone. For optimal performance, PRS should be developed for use in the specific ethnic groups to which they are to be applied. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.EnglishAll Open Access; Hybrid Gold Open AccessAdultAsian Continental Ancestry GroupBack PainC-Reactive ProteinCase-Control StudiesChronic PainEuropean Continental Ancestry GroupFemaleHLA-B27 AntigenHumansMagnetic Resonance ImagingMaleMultifactorial InheritanceReproducibility of ResultsRisk FactorsSacroiliac JointSpondylitis, AnkylosingC reactive proteinHLA B27 antigenC reactive proteinHLA B27 antigenadultageankylosing spondylitisArticlebackachechronic paincohort analysiscommunitycontrolled studydiagnostic testdiscriminant analysisdisease classificationEast AsianEuropeanfemalegenetic risk scoregenome-wide association studyhumanhypothesisintermethod comparisonmajor clinical studymalemicroarray analysisNew York criterianuclear magnetic resonance imagingpredictive valueprobabilityprotein blood levelreceiver operating characteristicsacroiliac jointsingle nucleotide polymorphismspine radiographyvalidation studyankylosing spondylitisAsian continental ancestry groupbackachecase control studyCaucasianchronic paindiagnostic imaginggeneticsmetabolismmultifactorial inheritancereproducibilityrisk factorArticle10.1136/annrheumdis-2020-219446