title: Developing a Risk-scoring Model for Ankylosing Spondylitis Based on a Combination of HLA-B27, Single-nucleotide Polymorphism, and Copy Number Variant Markers.
abstract: To develop a genotype-based ankylosing spondylitis (AS) risk prediction model that is more sensitive and specific than HLA-B27 typing.
  
  
  
  To develop the AS genetic risk scoring (AS-GRS) model, 648 individuals (285 cases and 363 controls) were examined for 5 copy number variants (CNV), 7 single-nucleotide polymorphisms (SNP), and an HLA-B27 marker by TaqMan assays. The AS-GRS model was developed using logistic regression and validated with a larger independent set (576 cases and 680 controls).
  
  
  
  Through logistic regression, we built the AS-GRS model consisting of 5 genetic components: HLA-B27, 3 CNV (1q32.2, 13q13.1, and 16p13.3), and 1 SNP (rs10865331). All significant associations of genetic factors in the model were replicated in the independent validation set. The discriminative ability of the AS-GRS model measured by the area under the curve was excellent: 0.976 (95% CI 0.96-0.99) in the model construction set and 0.951 (95% CI 0.94-0.96) in the validation set. The AS-GRS model showed higher specificity and accuracy than the HLA-B27-only model when the sensitivity was set to over 94%. When we categorized the individuals into quartiles based on the AS-GRS scores, OR of the 4 groups (low, intermediate-1, intermediate-2, and high risk) showed an increasing trend with the AS-GRS scores (r2= 0.950) and the highest risk group showed a 494× higher risk of AS than the lowest risk group (95% CI 237.3-1029.1).
  
  
  
  Our AS-GRS could be used to identify individuals at high risk for AS before major symptoms appear, which may improve the prognosis for them through early treatment.
authors.affiliation: From the Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea, College of Medicine; Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea, College of Medicine; Hanyang University Hospital for Rheumatic Diseases; Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul; Division of Rheumatology, Daejeon Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, South Korea.|S.H. Jung, PhD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.M. Cho, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.H. Yim, MD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.H. Kim, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; H.C. Park, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; M.L. Cho, PhD, Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea; S.C. Shim, MD, PhD, Division of Rheumatology, Daejeon Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital; T.H. Kim, MD, PhD, Hanyang University Hospital for Rheumatic Diseases; S.H. Park, MD, PhD, Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital; Y.J. Chung, MD, PhD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Jung
authors.affiliation: From the Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea, College of Medicine; Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea, College of Medicine; Hanyang University Hospital for Rheumatic Diseases; Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul; Division of Rheumatology, Daejeon Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, South Korea.|S.H. Jung, PhD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.M. Cho, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.H. Yim, MD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.H. Kim, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; H.C. Park, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; M.L. Cho, PhD, Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea; S.C. Shim, MD, PhD, Division of Rheumatology, Daejeon Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital; T.H. Kim, MD, PhD, Hanyang University Hospital for Rheumatic Diseases; S.H. Park, MD, PhD, Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital; Y.J. Chung, MD, PhD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea.
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Cho
authors.affiliation: From the Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea, College of Medicine; Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea, College of Medicine; Hanyang University Hospital for Rheumatic Diseases; Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul; Division of Rheumatology, Daejeon Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, South Korea.|S.H. Jung, PhD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.M. Cho, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.H. Yim, MD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.H. Kim, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; H.C. Park, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; M.L. Cho, PhD, Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea; S.C. Shim, MD, PhD, Division of Rheumatology, Daejeon Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital; T.H. Kim, MD, PhD, Hanyang University Hospital for Rheumatic Diseases; S.H. Park, MD, PhD, Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital; Y.J. Chung, MD, PhD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea.
authors.forename: Seon-Hee
authors.initials: SH
authors.lastname: Yim
authors.affiliation: From the Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea, College of Medicine; Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea, College of Medicine; Hanyang University Hospital for Rheumatic Diseases; Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul; Division of Rheumatology, Daejeon Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, South Korea.|S.H. Jung, PhD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.M. Cho, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.H. Yim, MD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.H. Kim, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; H.C. Park, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; M.L. Cho, PhD, Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea; S.C. Shim, MD, PhD, Division of Rheumatology, Daejeon Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital; T.H. Kim, MD, PhD, Hanyang University Hospital for Rheumatic Diseases; S.H. Park, MD, PhD, Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital; Y.J. Chung, MD, PhD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea.
authors.forename: So-Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: From the Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea, College of Medicine; Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea, College of Medicine; Hanyang University Hospital for Rheumatic Diseases; Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul; Division of Rheumatology, Daejeon Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, South Korea.|S.H. Jung, PhD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.M. Cho, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.H. Yim, MD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.H. Kim, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; H.C. Park, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; M.L. Cho, PhD, Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea; S.C. Shim, MD, PhD, Division of Rheumatology, Daejeon Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital; T.H. Kim, MD, PhD, Hanyang University Hospital for Rheumatic Diseases; S.H. Park, MD, PhD, Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital; Y.J. Chung, MD, PhD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea.
authors.forename: Hyeon-Chun
authors.initials: HC
authors.lastname: Park
authors.affiliation: From the Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea, College of Medicine; Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea, College of Medicine; Hanyang University Hospital for Rheumatic Diseases; Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul; Division of Rheumatology, Daejeon Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, South Korea.|S.H. Jung, PhD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.M. Cho, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.H. Yim, MD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.H. Kim, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; H.C. Park, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; M.L. Cho, PhD, Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea; S.C. Shim, MD, PhD, Division of Rheumatology, Daejeon Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital; T.H. Kim, MD, PhD, Hanyang University Hospital for Rheumatic Diseases; S.H. Park, MD, PhD, Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital; Y.J. Chung, MD, PhD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea.
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
authors.affiliation: From the Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea, College of Medicine; Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea, College of Medicine; Hanyang University Hospital for Rheumatic Diseases; Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul; Division of Rheumatology, Daejeon Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, South Korea.|S.H. Jung, PhD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.M. Cho, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.H. Yim, MD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.H. Kim, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; H.C. Park, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; M.L. Cho, PhD, Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea; S.C. Shim, MD, PhD, Division of Rheumatology, Daejeon Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital; T.H. Kim, MD, PhD, Hanyang University Hospital for Rheumatic Diseases; S.H. Park, MD, PhD, Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital; Y.J. Chung, MD, PhD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea.
authors.forename: Seung-Cheol
authors.initials: SC
authors.lastname: Shim
authors.affiliation: From the Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea, College of Medicine; Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea, College of Medicine; Hanyang University Hospital for Rheumatic Diseases; Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul; Division of Rheumatology, Daejeon Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, South Korea.|S.H. Jung, PhD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.M. Cho, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.H. Yim, MD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.H. Kim, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; H.C. Park, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; M.L. Cho, PhD, Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea; S.C. Shim, MD, PhD, Division of Rheumatology, Daejeon Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital; T.H. Kim, MD, PhD, Hanyang University Hospital for Rheumatic Diseases; S.H. Park, MD, PhD, Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital; Y.J. Chung, MD, PhD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea.
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kim
authors.affiliation: From the Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea, College of Medicine; Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea, College of Medicine; Hanyang University Hospital for Rheumatic Diseases; Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul; Division of Rheumatology, Daejeon Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, South Korea.|S.H. Jung, PhD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.M. Cho, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.H. Yim, MD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.H. Kim, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; H.C. Park, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; M.L. Cho, PhD, Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea; S.C. Shim, MD, PhD, Division of Rheumatology, Daejeon Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital; T.H. Kim, MD, PhD, Hanyang University Hospital for Rheumatic Diseases; S.H. Park, MD, PhD, Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital; Y.J. Chung, MD, PhD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.affiliation: From the Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea, College of Medicine; Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea, College of Medicine; Hanyang University Hospital for Rheumatic Diseases; Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul; Division of Rheumatology, Daejeon Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital, Daejeon, South Korea. yejun@catholic.ac.kr.|S.H. Jung, PhD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.M. Cho, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.H. Yim, MD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; S.H. Kim, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; H.C. Park, MS, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea; M.L. Cho, PhD, Rheumatism Research Center, Catholic Research Institutes of Medical Science, The Catholic University of Korea; S.C. Shim, MD, PhD, Division of Rheumatology, Daejeon Rheumatoid and Degenerative Arthritis Center, Chungnam National University Hospital; T.H. Kim, MD, PhD, Hanyang University Hospital for Rheumatic Diseases; S.H. Park, MD, PhD, Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital; Y.J. Chung, MD, PhD, Integrated Research Center for Genome Polymorphism, Department of Microbiology, The Catholic University of Korea. yejun@catholic.ac.kr.
authors.forename: Yeun-Jun
authors.initials: YJ
authors.lastname: Chung
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D056915:DNA Copy Number Variations; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015796:HLA-B27 Antigen / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008962:Models, Theoretical; D020641:Polymorphism, Single Nucleotide; D013167:Spondylitis, Ankylosing / Q000235:genetics*; D055815:Young Adult
chemical_list: D015796:HLA-B27 Antigen
keywords: ANKYLOSING SPONDYLITIS; COPY NUMBER VARIATION; GENETIC RISK SCORING; HLA-B27; SINGLE-NUCLEOTIDE POLYMORPHISM