. 2021 Sep;80(9):1168-1174.

doi: 10.1136/annrheumdis-2020-219446. Epub 2021 Apr 20.

Polygenic Risk Scores have high diagnostic capacity in ankylosing spondylitis

Zhixiu Li^#¹, Xin Wu^#², Paul J Leo¹, Erika De Guzman³, Nurullah Akkoc⁴, Maxime Breban^{5

6

7}, Gary J Macfarlane^{8

9}, Mahdi Mahmoudi¹⁰, Helena Marzo-Ortega^{11

12}, Lisa K Anderson³, Lawrie Wheeler³, Chung-Tei Chou^{13

14}, Andrew A Harrison¹⁵, Simon Stebbings¹⁶, Gareth T Jones^{8

9}, So-Young Bang¹⁷, Geng Wang¹⁸, Ahmadreza Jamshidi¹⁰, Elham Farhadi¹⁰, Jing Song², Li Lin², Mengmeng Li², James Cheng-Chung Wei^{19

20

21}, Nicholas G Martin²², Margaret J Wright²³, MinJae Lee²⁴, Yuqin Wang²⁵, Jian Zhan²⁶, Jin-San Zhang^{27

28}, Xiaobing Wang²⁹, Zi-Bing Jin³⁰, Michael H Weisman³¹, Lianne S Gensler³², Michael M Ward³³, Mohammad Hossein Rahbar³⁴, Laura Diekman³⁵, Tae-Hwan Kim¹⁷, John D Reveille³⁵, Bryan Paul Wordsworth³⁶, Huji Xu^#^{37

38

39}, Matthew A Brown^#^{40

41}; TCRI AS Group

Collaborators, Affiliations

Collaborators

TCRI AS Group:
Jian Yin, Lei Jiang, Lin Zhou, Ting Li, Qingwen Wang, Tianwang Li, Guanmin Gao, Shengqian Xu, Weiguo Xiao, Hui Shen, Jingguo Zhou, Yuquan You, Dongbao Zhao, Qing Cai, Shengming Dai, Lan He, Ping Zhu, Zhenyu Jiang, Jian Xu, Huaxiang Wu, Lie Dai, Yang Li, Feng Ding, Xiaochun Zhu, Chongyang Liu, Dongyi He, Liyun Zhang, Zhijun Li, Futao Zhao, Hanshi Xu, Niansong Wang, Youlian Wang, Lindi Jiang, Yu Zhang, Jinwei Chen, Fang Cheng, Zhiyi Zhang, Yifang Mei, Liangjing Lv, Lingli Dong, Jing Yang, Yinong Li, Xiaodong Wang, Xiaofeng Li, Hongsheng Sun, Xianming Long, Xiao Zhang, Qinghong Yu, Xiaodan Kong, Yi Zheng, Miaojia Zhang, Yi Tao, Yisha Li, Xinwang Duan, Qianghua Wei, Xiaofei Wang, Jie Han, Rong Mu, Yiping Lin, Jian Zhu, Xiaoyuan Chen

Affiliations

¹ Queensland University of Technology, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Faculty of Health, Translational Research Institute, Woolloongabba, Queensland, Australia.
² Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, Shanghai, China.
³ Australian Translational Genomics Centre, Queensland University of Technology (QUT), Translational Research Institute, Woolloongabba, Queensland, Australia.
⁴ Department of Internal Medicine, Division of Rheumatology, School of Medicine, Manisa Celal Bayar University, Manisa, Turkey.
⁵ UMR 1173, Inserm, University of Versailles Saint-Quentin, Montigny-le-Bretonneux, France.
⁶ Service de Rhumatologie, Hôpital Ambroise Paré, Assistance Publique-Hôpitaux de Paris, Boulogne-Billancourt, France.
⁷ Laboratoire d'Excellence Inflamex, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
⁸ Epidemiology Group, Institute of Applied Health Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, Aberdeen, UK.
⁹ Aberdeen Centre for Arthritis and Musculoskeletal Health, University of Aberdeen, Foresterhill, Aberdeen, UK.
¹⁰ Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Tehran, Iran (the Islamic Republic of).
¹¹ NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
¹² Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
¹³ Division of Allergy, Immunology, Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
¹⁴ School of Medicine, National Yang-Ming University, Taipei, Taiwan.
¹⁵ Department of Medicine, University of Otago Wellington, Wellington, New Zealand.
¹⁶ Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
¹⁷ Hanyang University Hospital for Rheumatic Diseases, Hanyang University, Seoul, Korea (the Republic of).
¹⁸ University of Queensland Diamantina Institute, University of Queensland, Brisbane, Queensland, Australia.
¹⁹ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
²⁰ Department of Medicine, Chung Shan Medical University, Taichung, Taiwan.
²¹ Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
²² QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
²³ Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
²⁴ Population & Data Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
²⁵ State Key Laboratory of Optometry, Ophthalmology, and Vision Science, Affiliated Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
²⁶ Institute for Glycomics, Griffith University, Nathan, Queensland, Australia.
²⁷ Center for Precision Medicine, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
²⁸ Institute of Life Sciences, Wenzhou University, Wenzhou, Zhejiang, China.
²⁹ Rheumatology Department, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
³⁰ Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, Beijing, China.
³¹ Department of Medicine/Rheumatology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
³² Division of Medicine/Rheumatology, University of California San Francisco, San Francisco, California, USA.
³³ Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
³⁴ Internal Medicine, The University of Texas Health Science Center at Houston John P and Katherine G McGovern Medical School, Houston, Texas, USA.
³⁵ Department of Internal Medicine, Division of Rheumatology, McGovern Medical School at The University of Texas Health Science Center, Houston, Texas, USA.
³⁶ NIHR Oxford Musculoskeletal Biomedical Research Unit, Botnar Research Centre, University of Oxford, Oxford, Oxfordshire, UK.
³⁷ Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, Shanghai, China matt.brown@kcl.ac.uk xuhuji@smmu.edu.cn.
³⁸ School of Clinical Medicine, Tsinghua University, Beijing, Beijing, China.
³⁹ Peking-Tsinghua Center for Life Sciences, Tsinghua University, Beijing, China.
⁴⁰ Center for Precision Medicine, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China matt.brown@kcl.ac.uk xuhuji@smmu.edu.cn.
⁴¹ NIHR Biomedical Research Centre at Guy's and Saint Thomas' NHS Foundation Trust and King's College London, London, UK.

^# Contributed equally.

PMID: 34161253
PMCID: PMC8364478
DOI: 10.1136/annrheumdis-2020-219446

Polygenic Risk Scores have high diagnostic capacity in ankylosing spondylitis

Zhixiu Li et al. Ann Rheum Dis. 2021 Sep.

. 2021 Sep;80(9):1168-1174.

doi: 10.1136/annrheumdis-2020-219446. Epub 2021 Apr 20.

Authors

Collaborators

TCRI AS Group:
Jian Yin, Lei Jiang, Lin Zhou, Ting Li, Qingwen Wang, Tianwang Li, Guanmin Gao, Shengqian Xu, Weiguo Xiao, Hui Shen, Jingguo Zhou, Yuquan You, Dongbao Zhao, Qing Cai, Shengming Dai, Lan He, Ping Zhu, Zhenyu Jiang, Jian Xu, Huaxiang Wu, Lie Dai, Yang Li, Feng Ding, Xiaochun Zhu, Chongyang Liu, Dongyi He, Liyun Zhang, Zhijun Li, Futao Zhao, Hanshi Xu, Niansong Wang, Youlian Wang, Lindi Jiang, Yu Zhang, Jinwei Chen, Fang Cheng, Zhiyi Zhang, Yifang Mei, Liangjing Lv, Lingli Dong, Jing Yang, Yinong Li, Xiaodong Wang, Xiaofeng Li, Hongsheng Sun, Xianming Long, Xiao Zhang, Qinghong Yu, Xiaodan Kong, Yi Zheng, Miaojia Zhang, Yi Tao, Yisha Li, Xinwang Duan, Qianghua Wei, Xiaofei Wang, Jie Han, Rong Mu, Yiping Lin, Jian Zhu, Xiaoyuan Chen

Affiliations

¹ Queensland University of Technology, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Faculty of Health, Translational Research Institute, Woolloongabba, Queensland, Australia.
² Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, Shanghai, China.
³ Australian Translational Genomics Centre, Queensland University of Technology (QUT), Translational Research Institute, Woolloongabba, Queensland, Australia.
⁴ Department of Internal Medicine, Division of Rheumatology, School of Medicine, Manisa Celal Bayar University, Manisa, Turkey.
⁵ UMR 1173, Inserm, University of Versailles Saint-Quentin, Montigny-le-Bretonneux, France.
⁶ Service de Rhumatologie, Hôpital Ambroise Paré, Assistance Publique-Hôpitaux de Paris, Boulogne-Billancourt, France.
⁷ Laboratoire d'Excellence Inflamex, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
⁸ Epidemiology Group, Institute of Applied Health Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, Aberdeen, UK.
⁹ Aberdeen Centre for Arthritis and Musculoskeletal Health, University of Aberdeen, Foresterhill, Aberdeen, UK.
¹⁰ Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Tehran, Iran (the Islamic Republic of).
¹¹ NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
¹² Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
¹³ Division of Allergy, Immunology, Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
¹⁴ School of Medicine, National Yang-Ming University, Taipei, Taiwan.
¹⁵ Department of Medicine, University of Otago Wellington, Wellington, New Zealand.
¹⁶ Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
¹⁷ Hanyang University Hospital for Rheumatic Diseases, Hanyang University, Seoul, Korea (the Republic of).
¹⁸ University of Queensland Diamantina Institute, University of Queensland, Brisbane, Queensland, Australia.
¹⁹ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
²⁰ Department of Medicine, Chung Shan Medical University, Taichung, Taiwan.
²¹ Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
²² QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
²³ Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
²⁴ Population & Data Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
²⁵ State Key Laboratory of Optometry, Ophthalmology, and Vision Science, Affiliated Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
²⁶ Institute for Glycomics, Griffith University, Nathan, Queensland, Australia.
²⁷ Center for Precision Medicine, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
²⁸ Institute of Life Sciences, Wenzhou University, Wenzhou, Zhejiang, China.
²⁹ Rheumatology Department, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
³⁰ Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing, Beijing, China.
³¹ Department of Medicine/Rheumatology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
³² Division of Medicine/Rheumatology, University of California San Francisco, San Francisco, California, USA.
³³ Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
³⁴ Internal Medicine, The University of Texas Health Science Center at Houston John P and Katherine G McGovern Medical School, Houston, Texas, USA.
³⁵ Department of Internal Medicine, Division of Rheumatology, McGovern Medical School at The University of Texas Health Science Center, Houston, Texas, USA.
³⁶ NIHR Oxford Musculoskeletal Biomedical Research Unit, Botnar Research Centre, University of Oxford, Oxford, Oxfordshire, UK.
³⁷ Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, Shanghai, China matt.brown@kcl.ac.uk xuhuji@smmu.edu.cn.
³⁸ School of Clinical Medicine, Tsinghua University, Beijing, Beijing, China.
³⁹ Peking-Tsinghua Center for Life Sciences, Tsinghua University, Beijing, China.
⁴⁰ Center for Precision Medicine, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China matt.brown@kcl.ac.uk xuhuji@smmu.edu.cn.
⁴¹ NIHR Biomedical Research Centre at Guy's and Saint Thomas' NHS Foundation Trust and King's College London, London, UK.

^# Contributed equally.

PMID: 34161253
PMCID: PMC8364478
DOI: 10.1136/annrheumdis-2020-219446

Erratum in

Correction: Polygenic Risk Scores have high diagnostic capacity in ankylosing spondylitis.
[No authors listed] [No authors listed] Ann Rheum Dis. 2021 Nov;80(11):e187. doi: 10.1136/annrheumdis-2020-219446corr1. Ann Rheum Dis. 2021. PMID: 34642186 Free PMC article. No abstract available.

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.

Keywords: ankylosing; genetic; low back pain; magnetic resonance imaging; polymorphism; spondylitis.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None declared.

Figures

**Figure 1**
Receiver operating characteristic curve plot of performance of Polygenic Risk Scores (PRS) (purple dashes, area under the curve (AUC)=0.924), HLA-B27 (aqua dashes, AUC=0.869), PRS less major histocompatibility complex (MHC) (green line, AUC=0.782) and genome-wide significant loci only (red line, AUC=0.659).

**Figure 2**
Positive (PPV) and negative predictive values (NPV) of Polygenic Risk Scores (PRS) and HLA-B27 for ankylosing spondylitis (AS), assuming prior probability of AS of 30%, among Europeans. Centiles refer to the population distribution of the PRS.

See this image and copyright information in PMC

References

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Polygenic Risk Scores have high diagnostic capacity in ankylosing spondylitis

Collaborators

Affiliations

Polygenic Risk Scores have high diagnostic capacity in ankylosing spondylitis

Authors

Collaborators

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

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MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials

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