Open AccessJournal Article
Genetic diagnostic profiling in axial spondyloarthritis: a real world study
Gethin P. Thomas,Dana Willner,Philip Robinson,Adrian Cortes,Ran Duan,Martin Rudwaleit,Nurullah Akkoc,Jürgen Braun,C.T. Chou,Walter P. Maksymowych,Salih Ozgocmen,Euthalia Roussou,Joachim Sieper,Rafael Valle-Oñate,Désirée van der Heijde,James Cheng-Chung Wei,Paul Leo,Matthew A. Brown +17 more
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TLDR
In a clinical setting of referred back pain patients suspected to have axial SpA, genetic data was unable to use genetic data to construct a predictive model better than that based on existing clinical data.Abstract:
Objective Spondyloarthritis (SpA) is often diagnosed late in the course of the disease and improved methods for early diagnosis are required. We have tested the ability of genetic profiling to diagnose axial SpA (axSpA) as a whole group, or ankylosing spondylitis (AS) alone, in a cohort of chronic back pain patients. Methods 282 patients were recruited from centres in the United Kingdom, Germany, Taiwan, Canada, Columbia and Turkey as part of the ASAS classification criteria for axSpA study (ASAS cohort). Subjects were classified according to the ASAS axSpA criteria, and the modified New York Criteria for AS. Patients were genotyped for ~200,000 immune-mediated disease SNPs using the Illumina Immunochip. Results We first established the predictive accuracy of genetic data comparing 9,638 healthy controls and 4,428 AS cases from the homogenous International Genetics of AS (IGAS) Consortium Immunochip study which showed excellent predictive power (AUC=0.91). Genetic risk scores had lower predictive power (AUC=0.83) comparing ASAS cohort axSpA cases meeting the ASAS imaging criteria with IGAS controls. Comparing genetic risk scores showed moderate discriminatory capacity between IGAS AS and ASAS imaging positive cases (AUC 0.67±0.05), indicating that significant differences in genetic makeup exist between the cohorts. Conclusion In a clinical setting of referred back pain patients suspected to have axial SpA we were unable to use genetic data to construct a predictive model better than that based on existing clinical data. Potential confounding factors include significant heterogeneity in the ASAS cohort, possibly reflecting the disease heterogeneity of axSpA, or differences between centres in ascertainment or classification performance.read more
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Journal ArticleDOI
Axial spondyloarthritis: concept, construct, classification and implications for therapy
Philip Robinson,Philip Robinson,Sjef van der Linden,Sjef van der Linden,Muhammad Asim Khan,William J. Taylor +5 more
TL;DR: The axial spondyloarthritis (axSpA) disease concept has undergone substantial change from when the entity ankylosing sondylitis was defined by the modified New York criteria in 1984 as discussed by the authors.
Journal ArticleDOI
Genetics and Functional Genomics of Spondyloarthritis.
TL;DR: Current knowledge on genetic findings concerning SpA is summarized and strategic approaches for identification of additional variants are described, with a focus on rare variants in familial forms.
Journal ArticleDOI
Progress of genome-wide association studies of ankylosing spondylitis.
Zhixiu Li,Matthew A. Brown +1 more
TL;DR: The genetic variations associated with AS identified by GWAS, the major pathways revealed by these AS‐associated variations and critical cell types involved in AS development are discussed.
Journal ArticleDOI
Biomarker development for axial spondyloarthritis.
TL;DR: Improved biomarkers are needed for axial spondyloarthritis to assist with early diagnosis and to better predict treatment responses and long-term outcomes, and future developments to advance this field are suggested.
Journal ArticleDOI
Polygenic Risk Scores have high diagnostic capacity in ankylosing spondylitis.
Zhixiu Li,Xin Wu,Paul Leo,Erika De Guzman,Nurullah Akkoc,Maxime Breban,Maxime Breban,Gary J. Macfarlane,Mahdi Mahmoudi,Helena Marzo-Ortega,Helena Marzo-Ortega,Lisa Anderson,Lawrie Wheeler,Chung Tei Chou,Andrew A. Harrison,Simon Stebbings,Gareth T. Jones,So Young Bang,Geng Wang,Ahmadreza Jamshidi,Elham Farhadi,Jing Song,Li Lin,Mengmeng Li,James Cheng-Chung Wei,James Cheng-Chung Wei,Nicholas G. Martin,Margaret J. Wright,MinJae Lee,Yuqin Wang,Jian Zhan,Jin San Zhang,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 P Wordsworth,Huji Xu,Huji Xu,Matthew A. Brown,Matthew A. Brown +46 more
TL;DR: 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 this paper.
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