Polygenic Risk Scores have high diagnostic capacity in ankylosing spondylitis.
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Li Zhixiu, Wu Xin, Leo Paul J, De Guzman Erika, Akkoc Nurullah, Breban Maxime, Macfarlane Gary J, Mahmoudi Mahdi, Marzo-Ortega Helena, Anderson Lisa K, Wheeler Lawrie, Chou Chung-Tei, Harrison Andrew A, Stebbings Simon, Jones Gareth T, Bang So-Young, Wang Geng, Jamshidi Ahmadreza, Farhadi Elham, Song Jing, Lin Li, Li Mengmeng, Wei James Cheng-Chung, Martin Nicholas G, Wright Margaret J, Lee MinJae, Wang Yuqin, Zhan Jian, Zhang Jin-San, Wang Xiaobing, Jin Zi-Bing, Weisman Michael H, Gensler Lianne S, Ward Michael M, Rahbar Mohammad Hossein, Diekman Laura, Kim Tae-Hwan, Reveille John D, Wordsworth Bryan Paul, Xu Huji, Brown Matthew A, TCRI AS Group
Аннотация
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.