PT - JOURNAL ARTICLE AU - Zhixiu Li AU - Xin Wu AU - Paul J Leo AU - Erika De Guzman AU - Nurullah Akkoc AU - Maxime Breban AU - Gary J Macfarlane AU - Mahdi Mahmoudi AU - Helena Marzo-Ortega AU - Lisa K Anderson AU - Lawrie Wheeler AU - Chung-Tei Chou AU - Andrew A Harrison AU - Simon Stebbings AU - Gareth T Jones AU - So-Young Bang AU - Geng Wang AU - Ahmadreza Jamshidi AU - Elham Farhadi AU - Jing Song AU - Li Lin AU - Mengmeng Li AU - James Cheng-Chung Wei AU - Nicholas G Martin AU - Margaret J Wright AU - MinJae Lee AU - Yuqin Wang AU - Jian Zhan AU - Jin-San Zhang AU - Xiaobing Wang AU - Zi-Bing Jin AU - Michael H Weisman AU - Lianne S Gensler AU - Michael M Ward AU - Mohammad Hossein Rahbar AU - Laura Diekman AU - Tae-Hwan Kim AU - John D Reveille AU - Bryan Paul Wordsworth AU - Huji Xu AU - Matthew A Brown ED - , TI - Polygenic Risk Scores have high diagnostic capacity in ankylosing spondylitis AID - 10.1136/annrheumdis-2020-219446 DP - 2021 Sep 01 TA - Annals of the Rheumatic Diseases PG - 1168--1174 VI - 80 IP - 9 4099 - http://ard.bmj.com/content/80/9/1168.short 4100 - http://ard.bmj.com/content/80/9/1168.full SO - Ann Rheum Dis2021 Sep 01; 80 AB - Objective 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.All data relevant to the study are included in the article or uploaded as supplementary information. Details of the polygenic risk scores will be made available depending on completion of data transfer agreements with King's College London.