title: Genetic diagnostic profiling in axial spondyloarthritis: a real world study.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Queensland Diamantina Institute, Translational Research Institute, Brisbane; and Charles Sturt University, Wagga Wagga, New South Wales, Australia.
authors.forename: Gothic P
authors.initials: GP
authors.lastname: Thomas
authors.affiliation: University of Queensland Diamantina Institute, Translational Research Institute, Brisbane; and Australian Centre for Ecogenomics, School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia.
authors.forename: Dana
authors.initials: D
authors.lastname: Willner
authors.affiliation: University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Robinson
authors.affiliation: University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
authors.forename: Adrian
authors.initials: A
authors.lastname: Cortes
authors.affiliation: University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
authors.forename: Ran
authors.initials: R
authors.lastname: Duan
authors.affiliation: Klinikum Bielefeld and Charité University Medicine, Berlin, Germany; and Gent University, Gent, Belgium.
authors.forename: Martin
authors.initials: M
authors.lastname: Rudwaleit
authors.affiliation: Dokuz Eylul University Hospital, Izmir, Turkey.
authors.forename: Nurullah
authors.initials: N
authors.lastname: Akkoc
authors.affiliation: German Rheumatology Research Centre, Berlin, Germany.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Braun
authors.affiliation: Division of Allergy, Immunology, Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei; and School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chung-Tei
authors.initials: CT
authors.lastname: Chou
authors.affiliation: Department of Medicine, University of Alberta, Canada.
authors.forename: Walter P
authors.initials: WP
authors.lastname: Maksymowych
authors.affiliation: Division of Rheumatology, Department of Physical Medicine and Rehabilitation, Erciyes University, Faculty of Medicine, Kayseri, Turkey.
authors.forename: Salih
authors.initials: S
authors.lastname: Ozgocmen
authors.affiliation: King George Hospital, London, UK.
authors.forename: Euthalia
authors.initials: E
authors.lastname: Roussou
authors.affiliation: German Rheumatology Research Centre, Berlin; and Rheumatology, Med Klinik 1, Charite, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Sieper
authors.affiliation: Spondyloarthropathy Group-Division of Rheumatology, Hospital Militar Central/ Universidad de La Sabana, Colombia.
authors.forename: Rafael
authors.initials: R
authors.lastname: Valle-Oñate
authors.affiliation: Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Desiree
authors.initials: D
authors.lastname: van der Heijde
authors.affiliation: Chung Shan Medical University, Taichung, Taiwan.
authors.forename: James
authors.initials: J
authors.lastname: Wei
authors.affiliation: University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Leo
authors.affiliation: University of Queensland Diamantina Institute, Translational Research Institute; and Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Brown
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001416:Back Pain / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D002170:Canada; D016022:Case-Control Studies; D059350:Chronic Pain / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D003105:Colombia; D042241:Early Diagnosis; D005060:Europe; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005787:Gene Frequency; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007596:Joints / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012372:ROC Curve; D012307:Risk Factors; D013131:Spine / Q000503:physiopathology*; D013167:Spondylitis, Ankylosing / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D013624:Taiwan; D055815:Young Adult
chemical_list: D005819:Genetic Markers