Polygenic risk scores have high diagnostic capacity in ankylosing spondylitis

Zhixiu Li , Xin Wu , Paul J. Leo , Erika de Guzman, Nurullah Akkoc, Maxime Breban, Gary Macfarlane, Mahdi Mahmoudi, Helena Marzo-Ortega, Lisa Anderson, Lawrie Wheeler, Chung-Tei Chou, Andrew A. Harrison , Simon Stebbings , Gareth Jones, So-Young Bang, Geng Wang, Ahmadreza Jamshidi, Elham Farhadi, Jing SongLi Lin, Mengmeng Li, James Cheng-Chung Wei, Nicholas G Martin, Margaret J. Wright, MinJae Lee, Yuqin Wang, Jian Zhan, Jin-San Zhang, Xiaobing Wang, Zi-Bing Jin , Michael H. Weisman, Lianne S. Gensler, Michael M. Ward, Mohammad H. Rahbar, Laura Diekman, Tae-Hwan Kim, John D. Reveille, B. Paul Wordsworth, Huji Xu * (Corresponding Author), Matthew A. Brown * (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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We sought to test the hypothesis that polygenic risk scores (PRS) have strong capacity to discriminate cases of ankylosing spondylitis (AS) from healthy controls and individuals in the community with chronic back pain.
PRS 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 magnetic resonance imaging (MRI).
In people of European ethnicity, 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, 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, the maximum positive predictive value was 78.2% and negative predictive value 100%, whereas for HLA-B27 these values were 51.9% and 97.9% respectively.
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.

Original languageEnglish
Article numberannrheumdis-2020-219446
Pages (from-to)1168-1174
Number of pages7
JournalAnnals of the Rheumatic Diseases
Issue number9
Early online date20 Apr 2021
Publication statusPublished - 12 Aug 2021


  • Ankylosing spondylitis
  • Polygenic risk score
  • HLA-B27
  • CRP
  • MRI
  • Immunology
  • General Biochemistry, Genetics and Molecular Biology
  • Immunology and Allergy
  • Rheumatology


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