Polygenic Risk Scores have high diagnostic capacity in ankylosing spondylitis. Issue 9 (20th April 2021)

• Record Type: Journal Article
• Authors: 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;
• Other Names: author non-byline.; Yin Jian author non-byline.; Jiang Lei author non-byline.; Zhou Lin author non-byline.; Li Ting author non-byline.; Wang Qingwen author non-byline.; Li Tianwang author non-byline.; Gao Guanmin author non-byline.; Xu Shengqian author non-byline.; Xiao Weiguo author non-byline.; Shen Hui author non-byline.; Zhou Jingguo author non-byline.; You Yuquan author non-byline.; Zhao Dongbao author non-byline.; Cai Qing author non-byline.; Dai Shengming author non-byline.; He Lan author non-byline.; Zhu Ping author non-byline.; Jiang Zhenyu author non-byline.; Xu Jian author non-byline.; Wu Huaxiang author non-byline.; Dai Lie author non-byline.; Li Yang author non-byline.; Ding Feng author non-byline.; Zhu Xiaochun author non-byline.; Liu Chongyang author non-byline.; He Dongyi author non-byline.; Zhang Liyun author non-byline.; Li Zhijun author non-byline.; Zhao Futao author non-byline.; Xu Hanshi author non-byline.; Wang Niansong author non-byline.; Wang Youlian author non-byline.; Jiang Lindi author non-byline.; Zhang Yu author non-byline.; Chen Jinwei author non-byline.; Cheng Fang author non-byline.; Zhang Zhiyi author non-byline.; Mei Yifang author non-byline.; Lv Liangjing author non-byline.; Dong Lingli author non-byline.; Yang Jing author non-byline.; Li Yinong author non-byline.; Wang Xiaodong author non-byline.; Li Xiaofeng author non-byline.; Sun Hongsheng author non-byline.; Long Xianming author non-byline.; Zhang Xiao author non-byline.; Yu Qinghong author non-byline.; Kong Xiaodan author non-byline.; Zheng Yi author non-byline.; Zhang Miaojia author non-byline.; Tao Yi author non-byline.; Li Yisha author non-byline.; Duan Xinwang author non-byline.; Wei Qianghua author non-byline.; Wang Xiaofei author non-byline.; Han Jie author non-byline.; Mu Rong author non-byline.; Lin Yiping author non-byline.; Zhu Jian author non-byline.; Chen Xiaoyuan author non-byline.;
• Is Part Of: Annals of the rheumatic diseases. Volume 80:Issue 9(2021)
• Page Start: 1168
• Page End: 1174
• Publication Date: 2021-04-20
• Subjects: spondylitis -- ankylosing -- magnetic resonance imaging -- polymorphism -- genetic -- low back pain; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2020-219446
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : 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.